Intranet
Acces
Contact
Publications
2016 |
Paro, Simona; Imler, Jean-Luc Encyclopedia of Immunobiology Book Chapter Ratcliffe, M (Ed.): 1 , Chapitre “Immunity in insects”, p. 454-461, Elsevier, 2016. BibTeX | Étiquettes: imler, Immunity, Insect, M3i @inbook{Paro0000, title = {Encyclopedia of Immunobiology}, author = {Simona Paro and Jean-Luc Imler}, editor = {M Ratcliffe}, year = {2016}, date = {2016-08-01}, volume = {1}, pages = {454-461}, publisher = {Elsevier}, chapter = {“Immunity in insects”}, keywords = {imler, Immunity, Insect, M3i}, pubstate = {published}, tppubtype = {inbook} } |
2015 |
Veillard, Florian; Troxler, Laurent; Reichhart, Jean-Marc Drosophila melanogaster clip-domain serine proteases: Structure, function and regulation Article de journal Biochimie, 122 , p. 255-269, 2015, ISBN: 0300-9084. Résumé | Liens | BibTeX | Étiquettes: bioinformatic, Chymotrypsin, clip domain, Immunity, Insect, M3i, Melanization, reichhart, Serine Proteases, Serpin, Toll @article{veillard_drosophila_2015, title = {Drosophila melanogaster clip-domain serine proteases: Structure, function and regulation}, author = {Florian Veillard and Laurent Troxler and Jean-Marc Reichhart}, url = {http://www.sciencedirect.com/science/article/pii/S030090841500317X}, doi = {10.1016/j.biochi.2015.10.007}, isbn = {0300-9084}, year = {2015}, date = {2015-10-08}, journal = {Biochimie}, volume = {122}, pages = {255-269}, abstract = {Mammalian chymotrypsin-like serine proteases (SPs) are one of the best-studied family of enzymes with roles in a wide range of physiological processes, including digestion, blood coagulation, fibrinolysis and humoral immunity. Extracellular SPs can form cascades, in which one protease activates the zymogen of the next protease in the chain, to amplify physiological or pathological signals. These extracellular SPs are generally multi-domain proteins, with pro-domains that are involved in protein–protein interactions critical for the sequential organization of the cascades, the control of their intensity and their proper localization. Far less is known about invertebrate SPs than their mammalian counterparts. In insect genomes, SPs and their proteolytically inactive homologs (SPHs) constitute large protein families. In addition to the chymotrypsin fold, many of these proteins contain additional structural domains, often with conserved mammalian orthologues. However, the largest group of arthropod SP regulatory modules is the clip domains family, which has only been identified in arthropods. The clip-domain SPs are extracellular and have roles in the immune response and embryonic development. The powerful reverse-genetics tools in Drosophila melanogaster have been essential to identify the functions of clip-SPs and their organization in sequential cascades. This review focuses on the current knowledge of Drosophila clip-SPs and presents, when necessary, data obtained in other insect models. We will first cover the biochemical and structural features of clip domain SPs and SPHs. Clip-SPs are implicated in three main biological processes: the control of the dorso-ventral patterning during embryonic development; the activation of the Toll-mediated response to microbial infections and the prophenoloxydase cascade, which triggers melanization. Finally, we review the regulation of SPs and SPHs, from specificity of activation to inhibition by endogenous or pathogen-encoded inhibitors.}, keywords = {bioinformatic, Chymotrypsin, clip domain, Immunity, Insect, M3i, Melanization, reichhart, Serine Proteases, Serpin, Toll}, pubstate = {published}, tppubtype = {article} } Mammalian chymotrypsin-like serine proteases (SPs) are one of the best-studied family of enzymes with roles in a wide range of physiological processes, including digestion, blood coagulation, fibrinolysis and humoral immunity. Extracellular SPs can form cascades, in which one protease activates the zymogen of the next protease in the chain, to amplify physiological or pathological signals. These extracellular SPs are generally multi-domain proteins, with pro-domains that are involved in protein–protein interactions critical for the sequential organization of the cascades, the control of their intensity and their proper localization. Far less is known about invertebrate SPs than their mammalian counterparts. In insect genomes, SPs and their proteolytically inactive homologs (SPHs) constitute large protein families. In addition to the chymotrypsin fold, many of these proteins contain additional structural domains, often with conserved mammalian orthologues. However, the largest group of arthropod SP regulatory modules is the clip domains family, which has only been identified in arthropods. The clip-domain SPs are extracellular and have roles in the immune response and embryonic development. The powerful reverse-genetics tools in Drosophila melanogaster have been essential to identify the functions of clip-SPs and their organization in sequential cascades. This review focuses on the current knowledge of Drosophila clip-SPs and presents, when necessary, data obtained in other insect models. We will first cover the biochemical and structural features of clip domain SPs and SPHs. Clip-SPs are implicated in three main biological processes: the control of the dorso-ventral patterning during embryonic development; the activation of the Toll-mediated response to microbial infections and the prophenoloxydase cascade, which triggers melanization. Finally, we review the regulation of SPs and SPHs, from specificity of activation to inhibition by endogenous or pathogen-encoded inhibitors. |
Majzoub, Karim; Imler, Jean-Luc Encyclopedia of Molecular Cell Biology and Molecular Medicine Book Chapter Verlag, Wiley-VCH (Ed.): 1 , Chapitre « RNAi to treat virus infections », p. 192-228, GmbH & Co. KGaA, 2015. Résumé | Liens | BibTeX | Étiquettes: antiviral, Argonaute, Delivery, imler, Immunity, lipofection, M3i, microRNA (miRNA), RNA Virus Infections, RNAi, small hairpin RNA (shRNA), small interfering RNA (siRNA) @inbook{Majzoub2015, title = {Encyclopedia of Molecular Cell Biology and Molecular Medicine}, author = {Karim Majzoub and Jean-Luc Imler}, editor = {Wiley-VCH Verlag}, doi = {10.1002/3527600906.mcb.201500003}, year = {2015}, date = {2015-04-28}, volume = {1}, pages = {192-228}, publisher = {GmbH & Co. KGaA}, chapter = {« RNAi to treat virus infections »}, abstract = {In spite of its young age, the field of RNA interference has already yielded major advances in the laboratory. This sequence-specific mechanism of gene regulation also holds strong promise for the development of a new generation of drugs, in particular to control the everlasting threat of viral infections. Here, the mechanisms and pathways of RNA interference are reviewed, with emphasis placed on how RNA silencing forms a potent antiviral immune mechanism in plants and invertebrates. The approaches developed to use RNA interference to control viral infections in mammals are then described. Finally, the problems encountered while translating this revolutionary technology into the clinic are presented, and the advances currently developed to overcome these limitations are discussed.}, keywords = {antiviral, Argonaute, Delivery, imler, Immunity, lipofection, M3i, microRNA (miRNA), RNA Virus Infections, RNAi, small hairpin RNA (shRNA), small interfering RNA (siRNA)}, pubstate = {published}, tppubtype = {inbook} } In spite of its young age, the field of RNA interference has already yielded major advances in the laboratory. This sequence-specific mechanism of gene regulation also holds strong promise for the development of a new generation of drugs, in particular to control the everlasting threat of viral infections. Here, the mechanisms and pathways of RNA interference are reviewed, with emphasis placed on how RNA silencing forms a potent antiviral immune mechanism in plants and invertebrates. The approaches developed to use RNA interference to control viral infections in mammals are then described. Finally, the problems encountered while translating this revolutionary technology into the clinic are presented, and the advances currently developed to overcome these limitations are discussed. |
2014 |
Bonnay, François; Nguyen, Xuan-Hung; Cohen-Berros, Eva; Troxler, Laurent; Batsche, Eric; Camonis, Jacques; Takeuchi, Osamu; Reichhart, Jean-Marc; Matt, Nicolas Akirin specifies NF-κB selectivity of Drosophila innate immune response via chromatin remodeling Article de journal EMBO J., 33 (20), p. 2349–2362, 2014, ISSN: 1460-2075. Résumé | Liens | BibTeX | Étiquettes: Animals, bioinformatic, Cell Cycle Proteins, Chromatin Assembly and Disassembly, chromatin remodeling, DNA-Binding Proteins, Female, Genetic, Immunity, Innate, Innate immune response, M3i, Male, matt, Mutation, NF-kappa B, NF‐κB, Promoter Regions, proteomics, reichhart, Trans-Activators, Transcription Factors, Transcriptional Activation, Two-Hybrid System Techniques @article{bonnay_akirin_2014, title = {Akirin specifies NF-κB selectivity of Drosophila innate immune response via chromatin remodeling}, author = {François Bonnay and Xuan-Hung Nguyen and Eva Cohen-Berros and Laurent Troxler and Eric Batsche and Jacques Camonis and Osamu Takeuchi and Jean-Marc Reichhart and Nicolas Matt}, doi = {10.15252/embj.201488456}, issn = {1460-2075}, year = {2014}, date = {2014-10-01}, journal = {EMBO J.}, volume = {33}, number = {20}, pages = {2349--2362}, abstract = {The network of NF-κB-dependent transcription that activates both pro- and anti-inflammatory genes in mammals is still unclear. As NF-κB factors are evolutionarily conserved, we used Drosophila to understand this network. The NF-κB transcription factor Relish activates effector gene expression following Gram-negative bacterial immune challenge. Here, we show, using a genome-wide approach, that the conserved nuclear protein Akirin is a NF-κB co-factor required for the activation of a subset of Relish-dependent genes correlating with the presence of H3K4ac epigenetic marks. A large-scale unbiased proteomic analysis revealed that Akirin orchestrates NF-κB transcriptional selectivity through the recruitment of the Osa-containing-SWI/SNF-like Brahma complex (BAP). Immune challenge in Drosophila shows that Akirin is required for the transcription of a subset of effector genes, but dispensable for the transcription of genes that are negative regulators of the innate immune response. Therefore, Akirins act as molecular selectors specifying the choice between subsets of NF-κB target genes. The discovery of this mechanism, conserved in mammals, paves the way for the establishment of more specific and less toxic anti-inflammatory drugs targeting pro-inflammatory genes.}, keywords = {Animals, bioinformatic, Cell Cycle Proteins, Chromatin Assembly and Disassembly, chromatin remodeling, DNA-Binding Proteins, Female, Genetic, Immunity, Innate, Innate immune response, M3i, Male, matt, Mutation, NF-kappa B, NF‐κB, Promoter Regions, proteomics, reichhart, Trans-Activators, Transcription Factors, Transcriptional Activation, Two-Hybrid System Techniques}, pubstate = {published}, tppubtype = {article} } The network of NF-κB-dependent transcription that activates both pro- and anti-inflammatory genes in mammals is still unclear. As NF-κB factors are evolutionarily conserved, we used Drosophila to understand this network. The NF-κB transcription factor Relish activates effector gene expression following Gram-negative bacterial immune challenge. Here, we show, using a genome-wide approach, that the conserved nuclear protein Akirin is a NF-κB co-factor required for the activation of a subset of Relish-dependent genes correlating with the presence of H3K4ac epigenetic marks. A large-scale unbiased proteomic analysis revealed that Akirin orchestrates NF-κB transcriptional selectivity through the recruitment of the Osa-containing-SWI/SNF-like Brahma complex (BAP). Immune challenge in Drosophila shows that Akirin is required for the transcription of a subset of effector genes, but dispensable for the transcription of genes that are negative regulators of the innate immune response. Therefore, Akirins act as molecular selectors specifying the choice between subsets of NF-κB target genes. The discovery of this mechanism, conserved in mammals, paves the way for the establishment of more specific and less toxic anti-inflammatory drugs targeting pro-inflammatory genes. |
Tartey, Sarang; Matsushita, Kazufumi; Vandenbon, Alexis; Ori, Daisuke; Imamura, Tomoko; Mino, Takashi; Standley, Daron M; Hoffmann, Jules A; Reichhart, Jean-Marc; Akira, Shizuo; Takeuchi, Osamu Akirin2 is critical for inducing inflammatory genes by bridging IκB-ζ and the SWI/SNF complex Article de journal EMBO J., 33 (20), p. 2332–2348, 2014, ISSN: 1460-2075. Résumé | Liens | BibTeX | Étiquettes: Adaptor Proteins, Animals, Cell Nucleus, Chromatin Assembly and Disassembly, chromatin remodeling, Chromosomal Proteins, cytokine, Cytokines, Female, Gene Expression Regulation, gene regulation, Genetic, hoffmann, Humans, Immunity, Innate, innate immunity, Knockout, Listeria monocytogenes, M3i, Macrophages, Male, Mice, Multiprotein Complexes, Non-Histone, Nuclear Proteins, Promoter Regions, Protein Binding, reichhart, Repressor Proteins, Sequence Deletion, Signal Transducing, Transcriptional Activation @article{tartey_akirin2_2014, title = {Akirin2 is critical for inducing inflammatory genes by bridging IκB-ζ and the SWI/SNF complex}, author = {Sarang Tartey and Kazufumi Matsushita and Alexis Vandenbon and Daisuke Ori and Tomoko Imamura and Takashi Mino and Daron M Standley and Jules A Hoffmann and Jean-Marc Reichhart and Shizuo Akira and Osamu Takeuchi}, doi = {10.15252/embj.201488447}, issn = {1460-2075}, year = {2014}, date = {2014-10-01}, journal = {EMBO J.}, volume = {33}, number = {20}, pages = {2332--2348}, abstract = {Transcription of inflammatory genes in innate immune cells is coordinately regulated by transcription factors, including NF-κB, and chromatin modifiers. However, it remains unclear how microbial sensing initiates chromatin remodeling. Here, we show that Akirin2, an evolutionarily conserved nuclear protein, bridges NF-κB and the chromatin remodeling SWI/SNF complex by interacting with BRG1-Associated Factor 60 (BAF60) proteins as well as IκB-ζ, which forms a complex with the NF-κB p50 subunit. These interactions are essential for Toll-like receptor-, RIG-I-, and Listeria-mediated expression of proinflammatory genes including Il6 and Il12b in macrophages. Consistently, effective clearance of Listeria infection required Akirin2. Furthermore, Akirin2 and IκB-ζ recruitment to the Il6 promoter depend upon the presence of IκB-ζ and Akirin2, respectively, for regulation of chromatin remodeling. BAF60 proteins were also essential for the induction of Il6 in response to LPS stimulation. Collectively, the IκB-ζ-Akirin2-BAF60 complex physically links the NF-κB and SWI/SNF complexes in innate immune cell activation. By recruiting SWI/SNF chromatin remodellers to IκB-ζ, transcriptional coactivator for NF-κB, the conserved nuclear protein Akirin2 stimulates pro-inflammatory gene promoters in mouse macrophages during innate immune responses to viral or bacterial infection.}, keywords = {Adaptor Proteins, Animals, Cell Nucleus, Chromatin Assembly and Disassembly, chromatin remodeling, Chromosomal Proteins, cytokine, Cytokines, Female, Gene Expression Regulation, gene regulation, Genetic, hoffmann, Humans, Immunity, Innate, innate immunity, Knockout, Listeria monocytogenes, M3i, Macrophages, Male, Mice, Multiprotein Complexes, Non-Histone, Nuclear Proteins, Promoter Regions, Protein Binding, reichhart, Repressor Proteins, Sequence Deletion, Signal Transducing, Transcriptional Activation}, pubstate = {published}, tppubtype = {article} } Transcription of inflammatory genes in innate immune cells is coordinately regulated by transcription factors, including NF-κB, and chromatin modifiers. However, it remains unclear how microbial sensing initiates chromatin remodeling. Here, we show that Akirin2, an evolutionarily conserved nuclear protein, bridges NF-κB and the chromatin remodeling SWI/SNF complex by interacting with BRG1-Associated Factor 60 (BAF60) proteins as well as IκB-ζ, which forms a complex with the NF-κB p50 subunit. These interactions are essential for Toll-like receptor-, RIG-I-, and Listeria-mediated expression of proinflammatory genes including Il6 and Il12b in macrophages. Consistently, effective clearance of Listeria infection required Akirin2. Furthermore, Akirin2 and IκB-ζ recruitment to the Il6 promoter depend upon the presence of IκB-ζ and Akirin2, respectively, for regulation of chromatin remodeling. BAF60 proteins were also essential for the induction of Il6 in response to LPS stimulation. Collectively, the IκB-ζ-Akirin2-BAF60 complex physically links the NF-κB and SWI/SNF complexes in innate immune cell activation. By recruiting SWI/SNF chromatin remodellers to IκB-ζ, transcriptional coactivator for NF-κB, the conserved nuclear protein Akirin2 stimulates pro-inflammatory gene promoters in mouse macrophages during innate immune responses to viral or bacterial infection. |
Lamiable, Olivier; Imler, Jean-Luc Induced antiviral innate immunity in Drosophila Article de journal Current Opinion in Microbiology, 20 , p. 62–68, 2014, ISSN: 1879-0364. Résumé | Liens | BibTeX | Étiquettes: Animals, Gene Expression Regulation, Host-Pathogen Interactions, imler, Immunity, Innate, M3i, RNA Viruses, Signal Transduction @article{lamiable_induced_2014, title = {Induced antiviral innate immunity in Drosophila}, author = {Olivier Lamiable and Jean-Luc Imler}, doi = {10.1016/j.mib.2014.05.006}, issn = {1879-0364}, year = {2014}, date = {2014-08-01}, journal = {Current Opinion in Microbiology}, volume = {20}, pages = {62--68}, abstract = {Immunity to viral infections in the model organism Drosophila melanogaster involves both RNA interference and additional induced responses. The latter include not only cellular mechanisms such as programmed cell death and autophagy, but also the induction of a large set of genes, some of which contribute to the control of viral replication and resistance to infection. This induced response to infection is complex and involves both virus-specific and cell-type specific mechanisms. We review here recent developments, from the sensing of viral infection to the induction of signaling pathways and production of antiviral effector molecules. Our current understanding, although still partial, validates the Drosophila model of antiviral induced immunity for insect pests and disease vectors, as well as for mammals.}, keywords = {Animals, Gene Expression Regulation, Host-Pathogen Interactions, imler, Immunity, Innate, M3i, RNA Viruses, Signal Transduction}, pubstate = {published}, tppubtype = {article} } Immunity to viral infections in the model organism Drosophila melanogaster involves both RNA interference and additional induced responses. The latter include not only cellular mechanisms such as programmed cell death and autophagy, but also the induction of a large set of genes, some of which contribute to the control of viral replication and resistance to infection. This induced response to infection is complex and involves both virus-specific and cell-type specific mechanisms. We review here recent developments, from the sensing of viral infection to the induction of signaling pathways and production of antiviral effector molecules. Our current understanding, although still partial, validates the Drosophila model of antiviral induced immunity for insect pests and disease vectors, as well as for mammals. |
Goto, Akira; Fukuyama, Hidehiro; Imler, Jean-Luc; Hoffmann, Jules A The chromatin regulator DMAP1 modulates activity of the nuclear factor B (NF-B) transcription factor Relish in the Drosophila innate immune response Article de journal The Journal of Biological Chemistry, 289 (30), p. 20470–20476, 2014, ISSN: 1083-351X. Résumé | Liens | BibTeX | Étiquettes: Animals, Cell Line, Chromatin Assembly and Disassembly, Epistasis, Escherichia coli, Escherichia coli Infections, Genetic, hoffmann, imler, Immunity, Innate, M3i, NF-kappa B, Repressor Proteins, Signal Transduction, Transcription Factors @article{goto_chromatin_2014, title = {The chromatin regulator DMAP1 modulates activity of the nuclear factor B (NF-B) transcription factor Relish in the Drosophila innate immune response}, author = {Akira Goto and Hidehiro Fukuyama and Jean-Luc Imler and Jules A Hoffmann}, doi = {10.1074/jbc.C114.553719}, issn = {1083-351X}, year = {2014}, date = {2014-07-01}, journal = {The Journal of Biological Chemistry}, volume = {289}, number = {30}, pages = {20470--20476}, abstract = {The host defense of the model organism Drosophila is under the control of two major signaling cascades controlling transcription factors of the NF-B family, the Toll and the immune deficiency (IMD) pathways. The latter shares extensive similarities with the mammalian TNF-R pathway and was initially discovered for its role in anti-Gram-negative bacterial reactions. A previous interactome study from this laboratory reported that an unexpectedly large number of proteins are binding to the canonical components of the IMD pathway. Here, we focus on DNA methyltransferase-associated protein 1 (DMAP1), which this study identified as an interactant of Relish, a Drosophila transcription factor reminiscent of the mammalian p105 NF-B protein. We show that silencing of DMAP1 expression both in S2 cells and in flies results in a significant reduction of Escherichia coli-induced expression of antimicrobial peptides. Epistatic analysis indicates that DMAP1 acts in parallel or downstream of Relish. Co-immunoprecipitation experiments further reveal that, in addition to Relish, DMAP1 also interacts with Akirin and the Brahma-associated protein 55 kDa (BAP55). Taken together, these results reveal that DMAP1 is a novel nuclear modulator of the IMD pathway, possibly acting at the level of chromatin remodeling.}, keywords = {Animals, Cell Line, Chromatin Assembly and Disassembly, Epistasis, Escherichia coli, Escherichia coli Infections, Genetic, hoffmann, imler, Immunity, Innate, M3i, NF-kappa B, Repressor Proteins, Signal Transduction, Transcription Factors}, pubstate = {published}, tppubtype = {article} } The host defense of the model organism Drosophila is under the control of two major signaling cascades controlling transcription factors of the NF-B family, the Toll and the immune deficiency (IMD) pathways. The latter shares extensive similarities with the mammalian TNF-R pathway and was initially discovered for its role in anti-Gram-negative bacterial reactions. A previous interactome study from this laboratory reported that an unexpectedly large number of proteins are binding to the canonical components of the IMD pathway. Here, we focus on DNA methyltransferase-associated protein 1 (DMAP1), which this study identified as an interactant of Relish, a Drosophila transcription factor reminiscent of the mammalian p105 NF-B protein. We show that silencing of DMAP1 expression both in S2 cells and in flies results in a significant reduction of Escherichia coli-induced expression of antimicrobial peptides. Epistatic analysis indicates that DMAP1 acts in parallel or downstream of Relish. Co-immunoprecipitation experiments further reveal that, in addition to Relish, DMAP1 also interacts with Akirin and the Brahma-associated protein 55 kDa (BAP55). Taken together, these results reveal that DMAP1 is a novel nuclear modulator of the IMD pathway, possibly acting at the level of chromatin remodeling. |
Imler, Jean-Luc Overview of Drosophila immunity: a historical perspective Article de journal Developmental and Comparative Immunology, 42 (1), p. 3–15, 2014, ISSN: 1879-0089. Résumé | Liens | BibTeX | Étiquettes: Allergy and Immunology, Animal, Animals, Antimicrobial Cationic Peptides, Antimicrobial peptides, history, Humans, IMD pathway, imler, Immunity, Innate, innate immunity, M3i, Models, Pattern recognition receptors, Signal Transduction, Toll-Like Receptors @article{imler_overview_2014, title = {Overview of Drosophila immunity: a historical perspective}, author = {Jean-Luc Imler}, doi = {10.1016/j.dci.2013.08.018}, issn = {1879-0089}, year = {2014}, date = {2014-01-01}, journal = {Developmental and Comparative Immunology}, volume = {42}, number = {1}, pages = {3--15}, abstract = {The functional analysis of genes from the model organism Drosophila melanogaster has provided invaluable information for many cellular and developmental or physiological processes, including immunity. The best-understood aspect of Drosophila immunity is the inducible humoral response, first recognized in 1972. This pioneering work led to a remarkable series of findings over the next 30 years, ranging from the identification and characterization of the antimicrobial peptides produced, to the deciphering of the signalling pathways activating the genes that encode them and, ultimately, to the discovery of the receptors sensing infection. These studies on an insect model coincided with a revival of the field of innate immunity, and had an unanticipated impact on the biomedical field.}, keywords = {Allergy and Immunology, Animal, Animals, Antimicrobial Cationic Peptides, Antimicrobial peptides, history, Humans, IMD pathway, imler, Immunity, Innate, innate immunity, M3i, Models, Pattern recognition receptors, Signal Transduction, Toll-Like Receptors}, pubstate = {published}, tppubtype = {article} } The functional analysis of genes from the model organism Drosophila melanogaster has provided invaluable information for many cellular and developmental or physiological processes, including immunity. The best-understood aspect of Drosophila immunity is the inducible humoral response, first recognized in 1972. This pioneering work led to a remarkable series of findings over the next 30 years, ranging from the identification and characterization of the antimicrobial peptides produced, to the deciphering of the signalling pathways activating the genes that encode them and, ultimately, to the discovery of the receptors sensing infection. These studies on an insect model coincided with a revival of the field of innate immunity, and had an unanticipated impact on the biomedical field. |
2013 |
Ferrandon, Dominique The complementary facets of epithelial host defenses in the genetic model organism Drosophila melanogaster: from resistance to resilience Article de journal Curr. Opin. Immunol., 25 (1), p. 59–70, 2013, ISSN: 1879-0372. Résumé | Liens | BibTeX | Étiquettes: Adult Stem Cells, aging, Animal, Animals, Cell Proliferation, Disease Models, Enterocytes, ferrandon, Humans, Immunity, Intestinal Mucosa, M3i, Metagenome, Stem Cell Niche, Wound Healing @article{ferrandon_complementary_2013b, title = {The complementary facets of epithelial host defenses in the genetic model organism Drosophila melanogaster: from resistance to resilience}, author = {Dominique Ferrandon}, doi = {10.1016/j.coi.2012.11.008}, issn = {1879-0372}, year = {2013}, date = {2013-02-01}, journal = {Curr. Opin. Immunol.}, volume = {25}, number = {1}, pages = {59--70}, abstract = {Significant advances have been made in our understanding of the host defense against microbial infections taking place at frontier epithelia of Drosophila flies. Immune deficiency (IMD), the major NF-κB immune response pathway induced in these epithelia, displays remarkable adaptations in its activation and regulation in the respiratory and digestive tract. The host defense against ingested pathogens is not limited to resistance, that is, the immune response. It also involves resilience, the capacity of the host to endure and repair damages inflicted by pathogens or the host's own immune response. For instance, enterocytes damaged by pathogens, the microbiota of aging flies, or host-derived reactive oxygen species (ROS), are replaced under the control of multiple pathways by the compensatory proliferation of intestinal stem cells (ISCs).}, keywords = {Adult Stem Cells, aging, Animal, Animals, Cell Proliferation, Disease Models, Enterocytes, ferrandon, Humans, Immunity, Intestinal Mucosa, M3i, Metagenome, Stem Cell Niche, Wound Healing}, pubstate = {published}, tppubtype = {article} } Significant advances have been made in our understanding of the host defense against microbial infections taking place at frontier epithelia of Drosophila flies. Immune deficiency (IMD), the major NF-κB immune response pathway induced in these epithelia, displays remarkable adaptations in its activation and regulation in the respiratory and digestive tract. The host defense against ingested pathogens is not limited to resistance, that is, the immune response. It also involves resilience, the capacity of the host to endure and repair damages inflicted by pathogens or the host's own immune response. For instance, enterocytes damaged by pathogens, the microbiota of aging flies, or host-derived reactive oxygen species (ROS), are replaced under the control of multiple pathways by the compensatory proliferation of intestinal stem cells (ISCs). |
Baron, Olga Lucia; van West, Pieter; Industri, Benoit; Ponchet, Michel; Dubreuil, Géraldine; Gourbal, Benjamin; Reichhart, Jean-Marc; Coustau, Christine Parental transfer of the antimicrobial protein LBP/BPI protects Biomphalaria glabrata eggs against oomycete infections Article de journal PLoS Pathog., 9 (12), p. e1003792, 2013, ISSN: 1553-7374. Résumé | Liens | BibTeX | Étiquettes: Acute-Phase Proteins, Animals, Antimicrobial Cationic Peptides, Biomphalaria, Blood Proteins, Carrier Proteins, Cell Membrane, Cell Membrane Permeability, Cloning, Escherichia coli, Female, Immunity, infection, M3i, Maternally-Acquired, Membrane Glycoproteins, Microbial Sensitivity Tests, Molecular, Oomycetes, Recombinant Proteins, reichhart, Zygote @article{baron_parental_2013, title = {Parental transfer of the antimicrobial protein LBP/BPI protects Biomphalaria glabrata eggs against oomycete infections}, author = {Olga Lucia Baron and Pieter van West and Benoit Industri and Michel Ponchet and Géraldine Dubreuil and Benjamin Gourbal and Jean-Marc Reichhart and Christine Coustau}, doi = {10.1371/journal.ppat.1003792}, issn = {1553-7374}, year = {2013}, date = {2013-01-01}, journal = {PLoS Pathog.}, volume = {9}, number = {12}, pages = {e1003792}, abstract = {Vertebrate females transfer antibodies via the placenta, colostrum and milk or via the egg yolk to protect their immunologically immature offspring against pathogens. This evolutionarily important transfer of immunity is poorly documented in invertebrates and basic questions remain regarding the nature and extent of parental protection of offspring. In this study, we show that a lipopolysaccharide binding protein/bactericidal permeability increasing protein family member from the invertebrate Biomphalaria glabrata (BgLBP/BPI1) is massively loaded into the eggs of this freshwater snail. Native and recombinant proteins displayed conserved LPS-binding, antibacterial and membrane permeabilizing activities. A broad screening of various pathogens revealed a previously unknown biocidal activity of the protein against pathogenic water molds (oomycetes), which is conserved in human BPI. RNAi-dependent silencing of LBP/BPI in the parent snails resulted in a significant reduction of reproductive success and extensive death of eggs through oomycete infections. This work provides the first functional evidence that a LBP/BPI is involved in the parental immune protection of invertebrate offspring and reveals a novel and conserved biocidal activity for LBP/BPI family members.}, keywords = {Acute-Phase Proteins, Animals, Antimicrobial Cationic Peptides, Biomphalaria, Blood Proteins, Carrier Proteins, Cell Membrane, Cell Membrane Permeability, Cloning, Escherichia coli, Female, Immunity, infection, M3i, Maternally-Acquired, Membrane Glycoproteins, Microbial Sensitivity Tests, Molecular, Oomycetes, Recombinant Proteins, reichhart, Zygote}, pubstate = {published}, tppubtype = {article} } Vertebrate females transfer antibodies via the placenta, colostrum and milk or via the egg yolk to protect their immunologically immature offspring against pathogens. This evolutionarily important transfer of immunity is poorly documented in invertebrates and basic questions remain regarding the nature and extent of parental protection of offspring. In this study, we show that a lipopolysaccharide binding protein/bactericidal permeability increasing protein family member from the invertebrate Biomphalaria glabrata (BgLBP/BPI1) is massively loaded into the eggs of this freshwater snail. Native and recombinant proteins displayed conserved LPS-binding, antibacterial and membrane permeabilizing activities. A broad screening of various pathogens revealed a previously unknown biocidal activity of the protein against pathogenic water molds (oomycetes), which is conserved in human BPI. RNAi-dependent silencing of LBP/BPI in the parent snails resulted in a significant reduction of reproductive success and extensive death of eggs through oomycete infections. This work provides the first functional evidence that a LBP/BPI is involved in the parental immune protection of invertebrate offspring and reveals a novel and conserved biocidal activity for LBP/BPI family members. |
Ayyaz, Arshad; Giammarinaro, Philippe; Liégeois, Samuel; Lestradet, Matthieu; Ferrandon, Dominique Immunobiology, 218 (4), p. 635–644, 2013, ISSN: 1878-3279. Résumé | Liens | BibTeX | Étiquettes: Adaptor Proteins, Animal, Animals, Antigens, Differentiation, Disease Models, ferrandon, Immunity, Immunologic, Innate, Intestinal Diseases, M3i, Mucosal, Mutation, Receptors, Signal Transducing, Staphylococcal Infections, Staphylococcus, Starvation, Toll-Like Receptors @article{ayyaz_negative_2013b, title = {A negative role for MyD88 in the resistance to starvation as revealed in an intestinal infection of Drosophila melanogaster with the Gram-positive bacterium Staphylococcus xylosus}, author = {Arshad Ayyaz and Philippe Giammarinaro and Samuel Liégeois and Matthieu Lestradet and Dominique Ferrandon}, doi = {10.1016/j.imbio.2012.07.027}, issn = {1878-3279}, year = {2013}, date = {2013-01-01}, journal = {Immunobiology}, volume = {218}, number = {4}, pages = {635--644}, abstract = {Drosophila melanogaster is a useful model to investigate mucosal immunity. The immune response to intestinal infections is mediated partly by the Immune deficiency (IMD) pathway, which only gets activated by a type of peptidoglycan lacking in several medically important Gram-positive bacterial species such as Staphylococcus. Thus, the intestinal host defense against such bacterial strains remains poorly known. Here, we have used Staphylococcus xylosus to develop a model of intestinal infections by Gram-positive bacteria. S. xylosus behaves as an opportunistic pathogen in a septic injury model, being able to kill only flies immunodeficient either for the Toll pathway or the cellular response. When ingested, it is controlled by IMD-independent host intestinal defenses, yet flies eventually die. Having excluded an overreaction of the immune response and the action of toxins, we find that flies actually succumb to starvation, likely as a result of a competition for sucrose between the bacteria and the flies. Fat stores of wild-type flies are severely reduced within a day, a period when sucrose is not yet exhausted in the feeding solution. Interestingly, the Toll pathway mutant MyD88 is more resistant to the ingestion of S. xylosus and to starvation than wild-type flies. MyD88 flies do not rapidly deplete their fat stores when starved, in contrast to wild-type flies. Thus, we have uncovered a novel function of MyD88 in the regulation of metabolism that appears to be independent of its known roles in immunity and development.}, keywords = {Adaptor Proteins, Animal, Animals, Antigens, Differentiation, Disease Models, ferrandon, Immunity, Immunologic, Innate, Intestinal Diseases, M3i, Mucosal, Mutation, Receptors, Signal Transducing, Staphylococcal Infections, Staphylococcus, Starvation, Toll-Like Receptors}, pubstate = {published}, tppubtype = {article} } Drosophila melanogaster is a useful model to investigate mucosal immunity. The immune response to intestinal infections is mediated partly by the Immune deficiency (IMD) pathway, which only gets activated by a type of peptidoglycan lacking in several medically important Gram-positive bacterial species such as Staphylococcus. Thus, the intestinal host defense against such bacterial strains remains poorly known. Here, we have used Staphylococcus xylosus to develop a model of intestinal infections by Gram-positive bacteria. S. xylosus behaves as an opportunistic pathogen in a septic injury model, being able to kill only flies immunodeficient either for the Toll pathway or the cellular response. When ingested, it is controlled by IMD-independent host intestinal defenses, yet flies eventually die. Having excluded an overreaction of the immune response and the action of toxins, we find that flies actually succumb to starvation, likely as a result of a competition for sucrose between the bacteria and the flies. Fat stores of wild-type flies are severely reduced within a day, a period when sucrose is not yet exhausted in the feeding solution. Interestingly, the Toll pathway mutant MyD88 is more resistant to the ingestion of S. xylosus and to starvation than wild-type flies. MyD88 flies do not rapidly deplete their fat stores when starved, in contrast to wild-type flies. Thus, we have uncovered a novel function of MyD88 in the regulation of metabolism that appears to be independent of its known roles in immunity and development. |
2012 |
Deleury, Emeline; Dubreuil, Géraldine; Elangovan, Namasivayam; Wajnberg, Eric; Reichhart, Jean-Marc; Gourbal, Benjamin; Duval, David; Baron, Olga Lucia; Gouzy, Jérôme; Coustau, Christine Specific versus non-specific immune responses in an invertebrate species evidenced by a comparative de novo sequencing study Article de journal PLoS ONE, 7 (3), p. e32512, 2012, ISSN: 1932-6203. Résumé | Liens | BibTeX | Étiquettes: Animals, Biomphalaria, Calmodulin, Cluster Analysis, Complementary, DNA, Expressed Sequence Tags, Ferritins, Gene Expression Profiling, Gene Expression Regulation, High-Throughput Nucleotide Sequencing, Immunity, Innate, M3i, messenger, Pattern Recognition, Phylogeny, Receptors, reichhart, RNA, Signal Transduction, Zinc Fingers @article{deleury_specific_2012, title = {Specific versus non-specific immune responses in an invertebrate species evidenced by a comparative de novo sequencing study}, author = {Emeline Deleury and Géraldine Dubreuil and Namasivayam Elangovan and Eric Wajnberg and Jean-Marc Reichhart and Benjamin Gourbal and David Duval and Olga Lucia Baron and Jérôme Gouzy and Christine Coustau}, doi = {10.1371/journal.pone.0032512}, issn = {1932-6203}, year = {2012}, date = {2012-01-01}, journal = {PLoS ONE}, volume = {7}, number = {3}, pages = {e32512}, abstract = {Our present understanding of the functioning and evolutionary history of invertebrate innate immunity derives mostly from studies on a few model species belonging to ecdysozoa. In particular, the characterization of signaling pathways dedicated to specific responses towards fungi and Gram-positive or Gram-negative bacteria in Drosophila melanogaster challenged our original view of a non-specific immunity in invertebrates. However, much remains to be elucidated from lophotrochozoan species. To investigate the global specificity of the immune response in the fresh-water snail Biomphalaria glabrata, we used massive Illumina sequencing of 5'-end cDNAs to compare expression profiles after challenge by Gram-positive or Gram-negative bacteria or after a yeast challenge. 5'-end cDNA sequencing of the libraries yielded over 12 millions high quality reads. To link these short reads to expressed genes, we prepared a reference transcriptomic database through automatic assembly and annotation of the 758,510 redundant sequences (ESTs, mRNAs) of B. glabrata available in public databases. Computational analysis of Illumina reads followed by multivariate analyses allowed identification of 1685 candidate transcripts differentially expressed after an immune challenge, with a two fold ratio between transcripts showing a challenge-specific expression versus a lower or non-specific differential expression. Differential expression has been validated using quantitative PCR for a subset of randomly selected candidates. Predicted functions of annotated candidates (approx. 700 unisequences) belonged to a large extend to similar functional categories or protein types. This work significantly expands upon previous gene discovery and expression studies on B. glabrata and suggests that responses to various pathogens may involve similar immune processes or signaling pathways but different genes belonging to multigenic families. These results raise the question of the importance of gene duplication and acquisition of paralog functional diversity in the evolution of specific invertebrate immune responses.}, keywords = {Animals, Biomphalaria, Calmodulin, Cluster Analysis, Complementary, DNA, Expressed Sequence Tags, Ferritins, Gene Expression Profiling, Gene Expression Regulation, High-Throughput Nucleotide Sequencing, Immunity, Innate, M3i, messenger, Pattern Recognition, Phylogeny, Receptors, reichhart, RNA, Signal Transduction, Zinc Fingers}, pubstate = {published}, tppubtype = {article} } Our present understanding of the functioning and evolutionary history of invertebrate innate immunity derives mostly from studies on a few model species belonging to ecdysozoa. In particular, the characterization of signaling pathways dedicated to specific responses towards fungi and Gram-positive or Gram-negative bacteria in Drosophila melanogaster challenged our original view of a non-specific immunity in invertebrates. However, much remains to be elucidated from lophotrochozoan species. To investigate the global specificity of the immune response in the fresh-water snail Biomphalaria glabrata, we used massive Illumina sequencing of 5'-end cDNAs to compare expression profiles after challenge by Gram-positive or Gram-negative bacteria or after a yeast challenge. 5'-end cDNA sequencing of the libraries yielded over 12 millions high quality reads. To link these short reads to expressed genes, we prepared a reference transcriptomic database through automatic assembly and annotation of the 758,510 redundant sequences (ESTs, mRNAs) of B. glabrata available in public databases. Computational analysis of Illumina reads followed by multivariate analyses allowed identification of 1685 candidate transcripts differentially expressed after an immune challenge, with a two fold ratio between transcripts showing a challenge-specific expression versus a lower or non-specific differential expression. Differential expression has been validated using quantitative PCR for a subset of randomly selected candidates. Predicted functions of annotated candidates (approx. 700 unisequences) belonged to a large extend to similar functional categories or protein types. This work significantly expands upon previous gene discovery and expression studies on B. glabrata and suggests that responses to various pathogens may involve similar immune processes or signaling pathways but different genes belonging to multigenic families. These results raise the question of the importance of gene duplication and acquisition of paralog functional diversity in the evolution of specific invertebrate immune responses. |
2011 |
Limmer, Stefanie; Haller, Samantha; Drenkard, Eliana; Lee, Janice; Yu, Shen; Kocks, Christine; Ausubel, Frederick M; Ferrandon, Dominique Pseudomonas aeruginosa RhlR is required to neutralize the cellular immune response in a Drosophila melanogaster oral infection model Article de journal Proc. Natl. Acad. Sci. U.S.A., 108 (42), p. 17378–17383, 2011, ISSN: 1091-6490. Résumé | Liens | BibTeX | Étiquettes: Animal, Animals, Bacteremia, Bacterial Proteins, Cellular, Disease Models, ferrandon, Genes, Genetically Modified, Hemolymph, Host-Pathogen Interactions, Immunity, Insect, M3i, Mutation, Oral, Pseudomonas aeruginosa, Pseudomonas Infections, Quorum Sensing, Trans-Activators, Viral, Virulence @article{limmer_pseudomonas_2011b, title = {Pseudomonas aeruginosa RhlR is required to neutralize the cellular immune response in a Drosophila melanogaster oral infection model}, author = {Stefanie Limmer and Samantha Haller and Eliana Drenkard and Janice Lee and Shen Yu and Christine Kocks and Frederick M Ausubel and Dominique Ferrandon}, doi = {10.1073/pnas.1114907108}, issn = {1091-6490}, year = {2011}, date = {2011-10-01}, journal = {Proc. Natl. Acad. Sci. U.S.A.}, volume = {108}, number = {42}, pages = {17378--17383}, abstract = {An in-depth mechanistic understanding of microbial infection necessitates a molecular dissection of host-pathogen relationships. Both Drosophila melanogaster and Pseudomonas aeruginosa have been intensively studied. Here, we analyze the infection of D. melanogaster by P. aeruginosa by using mutants in both host and pathogen. We show that orally ingested P. aeruginosa crosses the intestinal barrier and then proliferates in the hemolymph, thereby causing the infected flies to die of bacteremia. Host defenses against ingested P. aeruginosa included an immune deficiency (IMD) response in the intestinal epithelium, systemic Toll and IMD pathway responses, and a cellular immune response controlling bacteria in the hemocoel. Although the observed cellular and intestinal immune responses appeared to act throughout the course of the infection, there was a late onset of the systemic IMD and Toll responses. In this oral infection model, P. aeruginosa PA14 did not require its type III secretion system or other well-studied virulence factors such as the two-component response regulator GacA or the protease AprA for virulence. In contrast, the quorum-sensing transcription factor RhlR, but surprisingly not LasR, played a key role in counteracting the cellular immune response against PA14, possibly at an early stage when only a few bacteria are present in the hemocoel. These results illustrate the power of studying infection from the dual perspective of host and pathogen by revealing that RhlR plays a more complex role during pathogenesis than previously appreciated.}, keywords = {Animal, Animals, Bacteremia, Bacterial Proteins, Cellular, Disease Models, ferrandon, Genes, Genetically Modified, Hemolymph, Host-Pathogen Interactions, Immunity, Insect, M3i, Mutation, Oral, Pseudomonas aeruginosa, Pseudomonas Infections, Quorum Sensing, Trans-Activators, Viral, Virulence}, pubstate = {published}, tppubtype = {article} } An in-depth mechanistic understanding of microbial infection necessitates a molecular dissection of host-pathogen relationships. Both Drosophila melanogaster and Pseudomonas aeruginosa have been intensively studied. Here, we analyze the infection of D. melanogaster by P. aeruginosa by using mutants in both host and pathogen. We show that orally ingested P. aeruginosa crosses the intestinal barrier and then proliferates in the hemolymph, thereby causing the infected flies to die of bacteremia. Host defenses against ingested P. aeruginosa included an immune deficiency (IMD) response in the intestinal epithelium, systemic Toll and IMD pathway responses, and a cellular immune response controlling bacteria in the hemocoel. Although the observed cellular and intestinal immune responses appeared to act throughout the course of the infection, there was a late onset of the systemic IMD and Toll responses. In this oral infection model, P. aeruginosa PA14 did not require its type III secretion system or other well-studied virulence factors such as the two-component response regulator GacA or the protease AprA for virulence. In contrast, the quorum-sensing transcription factor RhlR, but surprisingly not LasR, played a key role in counteracting the cellular immune response against PA14, possibly at an early stage when only a few bacteria are present in the hemocoel. These results illustrate the power of studying infection from the dual perspective of host and pathogen by revealing that RhlR plays a more complex role during pathogenesis than previously appreciated. |
Chtarbanova, Stanislava; Imler, Jean-Luc Microbial sensing by Toll receptors: a historical perspective Article de journal Arteriosclerosis, Thrombosis, and Vascular Biology, 31 (8), p. 1734–1738, 2011, ISSN: 1524-4636. Résumé | Liens | BibTeX | Étiquettes: Animals, Cardiovascular Diseases, history, Host-Pathogen Interactions, Humans, imler, Immunity, Innate, M3i, Macrophages, Toll-Like Receptors @article{chtarbanova_microbial_2011, title = {Microbial sensing by Toll receptors: a historical perspective}, author = {Stanislava Chtarbanova and Jean-Luc Imler}, doi = {10.1161/ATVBAHA.108.179523}, issn = {1524-4636}, year = {2011}, date = {2011-08-01}, journal = {Arteriosclerosis, Thrombosis, and Vascular Biology}, volume = {31}, number = {8}, pages = {1734--1738}, abstract = {The family of Toll-like receptors plays an essential role in the induction of the immune response. These receptors sense the presence of microbial ligands and activate the nuclear factor-κB transcription factor. We review the key studies that led from the formulation of the concept of pattern recognition receptors to the characterization of Toll-like receptors, insisting on the important role played by the model organism Drosophila melanogaster and on the increasing evidence connecting these receptors to cardiovascular disease.}, keywords = {Animals, Cardiovascular Diseases, history, Host-Pathogen Interactions, Humans, imler, Immunity, Innate, M3i, Macrophages, Toll-Like Receptors}, pubstate = {published}, tppubtype = {article} } The family of Toll-like receptors plays an essential role in the induction of the immune response. These receptors sense the presence of microbial ligands and activate the nuclear factor-κB transcription factor. We review the key studies that led from the formulation of the concept of pattern recognition receptors to the characterization of Toll-like receptors, insisting on the important role played by the model organism Drosophila melanogaster and on the increasing evidence connecting these receptors to cardiovascular disease. |
Eleftherianos, Ioannis; Won, Sungyong; Chtarbanova, Stanislava; Squiban, Barbara; Ocorr, Karen; Bodmer, Rolf; Beutler, Bruce; Hoffmann, Jules A; Imler, Jean-Luc ATP-sensitive potassium channel (K(ATP))-dependent regulation of cardiotropic viral infections Article de journal Proceedings of the National Academy of Sciences of the United States of America, 108 (29), p. 12024–12029, 2011, ISSN: 1091-6490. Résumé | Liens | BibTeX | Étiquettes: Animals, Heart, HeLa Cells, hoffmann, Humans, imler, Immunity, Immunoblotting, Inbred C57BL, Innate, KATP Channels, M3i, Mice, Nodaviridae, Pinacidil, Reverse Transcriptase Polymerase Chain Reaction, RNA Interference, Tolbutamide, Viral Load, Viremia @article{eleftherianos_atp-sensitive_2011, title = {ATP-sensitive potassium channel (K(ATP))-dependent regulation of cardiotropic viral infections}, author = {Ioannis Eleftherianos and Sungyong Won and Stanislava Chtarbanova and Barbara Squiban and Karen Ocorr and Rolf Bodmer and Bruce Beutler and Jules A Hoffmann and Jean-Luc Imler}, doi = {10.1073/pnas.1108926108}, issn = {1091-6490}, year = {2011}, date = {2011-07-01}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {108}, number = {29}, pages = {12024--12029}, abstract = {The effects of the cellular environment on innate immunity remain poorly characterized. Here, we show that in Drosophila ATP-sensitive potassium channels (K(ATP)) mediate resistance to a cardiotropic RNA virus, Flock House virus (FHV). FHV viral load in the heart rapidly increases in K(ATP) mutant flies, leading to increased viremia and accelerated death. The effect of K(ATP) channels is dependent on the RNA interference genes Dcr-2, AGO2, and r2d2, indicating that an activity associated with this potassium channel participates in this antiviral pathway in Drosophila. Flies treated with the K(ATP) agonist drug pinacidil are protected against FHV infection, thus demonstrating the importance of this regulation of innate immunity by the cellular environment in the heart. In mice, the Coxsackievirus B3 replicates to higher titers in the hearts of mayday mutant animals, which are deficient in the Kir6.1 subunit of K(ATP) channels, than in controls. Together, our data suggest that K(ATP) channel deregulation can have a critical impact on innate antiviral immunity in the heart.}, keywords = {Animals, Heart, HeLa Cells, hoffmann, Humans, imler, Immunity, Immunoblotting, Inbred C57BL, Innate, KATP Channels, M3i, Mice, Nodaviridae, Pinacidil, Reverse Transcriptase Polymerase Chain Reaction, RNA Interference, Tolbutamide, Viral Load, Viremia}, pubstate = {published}, tppubtype = {article} } The effects of the cellular environment on innate immunity remain poorly characterized. Here, we show that in Drosophila ATP-sensitive potassium channels (K(ATP)) mediate resistance to a cardiotropic RNA virus, Flock House virus (FHV). FHV viral load in the heart rapidly increases in K(ATP) mutant flies, leading to increased viremia and accelerated death. The effect of K(ATP) channels is dependent on the RNA interference genes Dcr-2, AGO2, and r2d2, indicating that an activity associated with this potassium channel participates in this antiviral pathway in Drosophila. Flies treated with the K(ATP) agonist drug pinacidil are protected against FHV infection, thus demonstrating the importance of this regulation of innate immunity by the cellular environment in the heart. In mice, the Coxsackievirus B3 replicates to higher titers in the hearts of mayday mutant animals, which are deficient in the Kir6.1 subunit of K(ATP) channels, than in controls. Together, our data suggest that K(ATP) channel deregulation can have a critical impact on innate antiviral immunity in the heart. |
Aoun, Richard Bou; Hetru, Charles; Troxler, Laurent; Doucet, Daniel; Ferrandon, Dominique; Matt, Nicolas Analysis of thioester-containing proteins during the innate immune response of Drosophila melanogaster Article de journal J Innate Immun, 3 (1), p. 52–64, 2011, ISSN: 1662-8128. Résumé | Liens | BibTeX | Étiquettes: Animals, bioinformatic, DNA, Evolution, ferrandon, Gene Expression Regulation, Hemocytes, Immunity, In Situ Hybridization, Innate, M3i, matt, Molecular, Mutation, Phylogeny, Sequence Analysis @article{bou_aoun_analysis_2011, title = {Analysis of thioester-containing proteins during the innate immune response of Drosophila melanogaster}, author = {Richard Bou Aoun and Charles Hetru and Laurent Troxler and Daniel Doucet and Dominique Ferrandon and Nicolas Matt}, doi = {10.1159/000321554}, issn = {1662-8128}, year = {2011}, date = {2011-01-01}, journal = {J Innate Immun}, volume = {3}, number = {1}, pages = {52--64}, abstract = {Thioester-containing proteins (TEPs) are conserved proteins among insects that are thought to be involved in innate immunity. In Drosophila, the Tep family is composed of 6 genes named Tep1-Tep6. In this study, we investigated the phylogeny, expression pattern and roles of these genes in the host defense of Drosophila. Protostomian Tep genes are clustered in 3 distinct branches, 1 of which is specific to mosquitoes. Most D. melanogaster Tep genes are expressed in hemocytes, can be induced in the fat body, and are expressed in specific regions of the hypodermis. This expression pattern is consistent with a role in innate immunity. However, we find that TEP1, TEP2, and TEP4 are not strictly required in the body cavity to fight several bacterial and fungal infections. One possibility is that Drosophila TEPs act redundantly or that their absence can be compensated by other components of the immune response. TEPs may thus provide a subtle selective advantage during evolution. Alternatively, they may be required in host defense against specific as yet unidentified natural pathogens of Drosophila.}, keywords = {Animals, bioinformatic, DNA, Evolution, ferrandon, Gene Expression Regulation, Hemocytes, Immunity, In Situ Hybridization, Innate, M3i, matt, Molecular, Mutation, Phylogeny, Sequence Analysis}, pubstate = {published}, tppubtype = {article} } Thioester-containing proteins (TEPs) are conserved proteins among insects that are thought to be involved in innate immunity. In Drosophila, the Tep family is composed of 6 genes named Tep1-Tep6. In this study, we investigated the phylogeny, expression pattern and roles of these genes in the host defense of Drosophila. Protostomian Tep genes are clustered in 3 distinct branches, 1 of which is specific to mosquitoes. Most D. melanogaster Tep genes are expressed in hemocytes, can be induced in the fat body, and are expressed in specific regions of the hypodermis. This expression pattern is consistent with a role in innate immunity. However, we find that TEP1, TEP2, and TEP4 are not strictly required in the body cavity to fight several bacterial and fungal infections. One possibility is that Drosophila TEPs act redundantly or that their absence can be compensated by other components of the immune response. TEPs may thus provide a subtle selective advantage during evolution. Alternatively, they may be required in host defense against specific as yet unidentified natural pathogens of Drosophila. |
Reichhart, Jean-Marc; Gubb, David; Leclerc, Vincent The Drosophila serpins: multiple functions in immunity and morphogenesis Article de journal Meth. Enzymol., 499 , p. 205–225, 2011, ISSN: 1557-7988. Résumé | Liens | BibTeX | Étiquettes: Animals, Immunity, Innate, M3i, Morphogenesis, reichhart, Serpins, Signal Transduction @article{reichhart_drosophila_2011, title = {The Drosophila serpins: multiple functions in immunity and morphogenesis}, author = {Jean-Marc Reichhart and David Gubb and Vincent Leclerc}, doi = {10.1016/B978-0-12-386471-0.00011-0}, issn = {1557-7988}, year = {2011}, date = {2011-01-01}, journal = {Meth. Enzymol.}, volume = {499}, pages = {205--225}, abstract = {Members of the serpin superfamily of proteins have been found in all living organisms, although rarely in bacteria or fungi. They have been extensively studied in mammals, where many rapid physiological responses are regulated by inhibitory serpins. In addition to the inhibitory serpins, a large group of noninhibitory proteins with a conserved serpin fold have also been identified in mammals. These noninhibitory proteins have a wide range of functions, from storage proteins to molecular chaperones, hormone transporters, and tumor suppressors. In contrast, until recently, very little was known about insect serpins in general, or Drosophila serpins in particular. In the last decade, however, there has been an increasing interest in the serpin biology of insects. It is becoming clear that, like in mammals, a similar wide range of physiological responses are regulated in insects and that noninhibitory serpin-fold proteins also play key roles in insect biology. Drosophila is also an important model organism that can be used to study human pathologies (among which serpinopathies or other protein conformational diseases) and mechanisms of regulation of proteolytic cascades in health or to develop strategies for control of insect pests and disease vectors. As most of our knowledge on insect serpins comes from studies on the Drosophila immune response, we survey here the Drosophila serpin literature and describe the laboratory techniques that have been developed to study serpin-regulated responses in this model genetic organism.}, keywords = {Animals, Immunity, Innate, M3i, Morphogenesis, reichhart, Serpins, Signal Transduction}, pubstate = {published}, tppubtype = {article} } Members of the serpin superfamily of proteins have been found in all living organisms, although rarely in bacteria or fungi. They have been extensively studied in mammals, where many rapid physiological responses are regulated by inhibitory serpins. In addition to the inhibitory serpins, a large group of noninhibitory proteins with a conserved serpin fold have also been identified in mammals. These noninhibitory proteins have a wide range of functions, from storage proteins to molecular chaperones, hormone transporters, and tumor suppressors. In contrast, until recently, very little was known about insect serpins in general, or Drosophila serpins in particular. In the last decade, however, there has been an increasing interest in the serpin biology of insects. It is becoming clear that, like in mammals, a similar wide range of physiological responses are regulated in insects and that noninhibitory serpin-fold proteins also play key roles in insect biology. Drosophila is also an important model organism that can be used to study human pathologies (among which serpinopathies or other protein conformational diseases) and mechanisms of regulation of proteolytic cascades in health or to develop strategies for control of insect pests and disease vectors. As most of our knowledge on insect serpins comes from studies on the Drosophila immune response, we survey here the Drosophila serpin literature and describe the laboratory techniques that have been developed to study serpin-regulated responses in this model genetic organism. |
Nehme, Nadine T; Quintin, Jessica; Cho, Ju Hyun; Lee, Janice; Lafarge, Marie-Céline; Kocks, Christine; Ferrandon, Dominique Relative roles of the cellular and humoral responses in the Drosophila host defense against three gram-positive bacterial infections Article de journal PLoS ONE, 6 (3), p. e14743, 2011, ISSN: 1932-6203. Résumé | Liens | BibTeX | Étiquettes: Animals, Antimicrobial Cationic Peptides, Carrier Proteins, Cell Surface, Cellular, Enterococcus faecalis, ferrandon, Gram-Positive Bacteria, Gram-Positive Bacterial Infections, Host-Pathogen Interactions, Humoral, Immunity, Innate, M3i, Micrococcus luteus, Opsonin Proteins, Phagocytosis, Receptors, Signal Transduction, Solubility, Staphylococcus aureus @article{nehme_relative_2011b, title = {Relative roles of the cellular and humoral responses in the Drosophila host defense against three gram-positive bacterial infections}, author = {Nadine T Nehme and Jessica Quintin and Ju Hyun Cho and Janice Lee and Marie-Céline Lafarge and Christine Kocks and Dominique Ferrandon}, doi = {10.1371/journal.pone.0014743}, issn = {1932-6203}, year = {2011}, date = {2011-01-01}, journal = {PLoS ONE}, volume = {6}, number = {3}, pages = {e14743}, abstract = {BACKGROUND: Two NF-kappaB signaling pathways, Toll and immune deficiency (imd), are required for survival to bacterial infections in Drosophila. In response to septic injury, these pathways mediate rapid transcriptional activation of distinct sets of effector molecules, including antimicrobial peptides, which are important components of a humoral defense response. However, it is less clear to what extent macrophage-like hemocytes contribute to host defense. METHODOLOGY/PRINCIPAL FINDINGS: In order to dissect the relative importance of humoral and cellular defenses after septic injury with three different gram-positive bacteria (Micrococcus luteus, Enterococcus faecalis, Staphylococcus aureus), we used latex bead pre-injection to ablate macrophage function in flies wildtype or mutant for various Toll and imd pathway components. We found that in all three infection models a compromised phagocytic system impaired fly survival--independently of concomitant Toll or imd pathway activation. Our data failed to confirm a role of the PGRP-SA and GNBP1 Pattern Recognition Receptors for phagocytosis of S. aureus. The Drosophila scavenger receptor Eater mediates the phagocytosis by hemocytes or S2 cells of E. faecalis and S. aureus, but not of M. luteus. In the case of M. luteus and E. faecalis, but not S. aureus, decreased survival due to defective phagocytosis could be compensated for by genetically enhancing the humoral immune response. CONCLUSIONS/SIGNIFICANCE: Our results underscore the fundamental importance of both cellular and humoral mechanisms in Drosophila immunity and shed light on the balance between these two arms of host defense depending on the invading pathogen.}, keywords = {Animals, Antimicrobial Cationic Peptides, Carrier Proteins, Cell Surface, Cellular, Enterococcus faecalis, ferrandon, Gram-Positive Bacteria, Gram-Positive Bacterial Infections, Host-Pathogen Interactions, Humoral, Immunity, Innate, M3i, Micrococcus luteus, Opsonin Proteins, Phagocytosis, Receptors, Signal Transduction, Solubility, Staphylococcus aureus}, pubstate = {published}, tppubtype = {article} } BACKGROUND: Two NF-kappaB signaling pathways, Toll and immune deficiency (imd), are required for survival to bacterial infections in Drosophila. In response to septic injury, these pathways mediate rapid transcriptional activation of distinct sets of effector molecules, including antimicrobial peptides, which are important components of a humoral defense response. However, it is less clear to what extent macrophage-like hemocytes contribute to host defense. METHODOLOGY/PRINCIPAL FINDINGS: In order to dissect the relative importance of humoral and cellular defenses after septic injury with three different gram-positive bacteria (Micrococcus luteus, Enterococcus faecalis, Staphylococcus aureus), we used latex bead pre-injection to ablate macrophage function in flies wildtype or mutant for various Toll and imd pathway components. We found that in all three infection models a compromised phagocytic system impaired fly survival--independently of concomitant Toll or imd pathway activation. Our data failed to confirm a role of the PGRP-SA and GNBP1 Pattern Recognition Receptors for phagocytosis of S. aureus. The Drosophila scavenger receptor Eater mediates the phagocytosis by hemocytes or S2 cells of E. faecalis and S. aureus, but not of M. luteus. In the case of M. luteus and E. faecalis, but not S. aureus, decreased survival due to defective phagocytosis could be compensated for by genetically enhancing the humoral immune response. CONCLUSIONS/SIGNIFICANCE: Our results underscore the fundamental importance of both cellular and humoral mechanisms in Drosophila immunity and shed light on the balance between these two arms of host defense depending on the invading pathogen. |
2010 |
Silverman, Gary A; Whisstock, James C; Bottomley, Stephen P; Huntington, James A; Kaiserman, Dion; Luke, Cliff J; Pak, Stephen C; Reichhart, Jean-Marc; Bird, Phillip I Serpins flex their muscle: I. Putting the clamps on proteolysis in diverse biological systems Article de journal J. Biol. Chem., 285 (32), p. 24299–24305, 2010, ISSN: 1083-351X. Résumé | Liens | BibTeX | Étiquettes: Animals, Biological, Caenorhabditis elegans, Cell Death, Cell Differentiation, Cell Survival, Homeostasis, Humans, Immunity, Innate, M3i, Mice, Models, Phenotype, reichhart, Serpins, Transgenes, transgenic @article{silverman_serpins_2010, title = {Serpins flex their muscle: I. Putting the clamps on proteolysis in diverse biological systems}, author = {Gary A Silverman and James C Whisstock and Stephen P Bottomley and James A Huntington and Dion Kaiserman and Cliff J Luke and Stephen C Pak and Jean-Marc Reichhart and Phillip I Bird}, doi = {10.1074/jbc.R110.112771}, issn = {1083-351X}, year = {2010}, date = {2010-08-01}, journal = {J. Biol. Chem.}, volume = {285}, number = {32}, pages = {24299--24305}, abstract = {Serpins compose the largest superfamily of peptidase inhibitors and are well known as regulators of hemostasis and thrombolysis. Studies using model organisms, from plants to vertebrates, now show that serpins and their unique inhibitory mechanism and conformational flexibility are exploited to control proteolysis in molecular pathways associated with cell survival, development, and host defense. In addition, an increasing number of non-inhibitory serpins are emerging as important elements within a diversity of biological systems by serving as chaperones, hormone transporters, or anti-angiogenic factors.}, keywords = {Animals, Biological, Caenorhabditis elegans, Cell Death, Cell Differentiation, Cell Survival, Homeostasis, Humans, Immunity, Innate, M3i, Mice, Models, Phenotype, reichhart, Serpins, Transgenes, transgenic}, pubstate = {published}, tppubtype = {article} } Serpins compose the largest superfamily of peptidase inhibitors and are well known as regulators of hemostasis and thrombolysis. Studies using model organisms, from plants to vertebrates, now show that serpins and their unique inhibitory mechanism and conformational flexibility are exploited to control proteolysis in molecular pathways associated with cell survival, development, and host defense. In addition, an increasing number of non-inhibitory serpins are emerging as important elements within a diversity of biological systems by serving as chaperones, hormone transporters, or anti-angiogenic factors. |
2009 |
Cronin, Shane J F; Nehme, Nadine T; Limmer, Stefanie; Liegeois, Samuel; Pospisilik, Andrew J; Schramek, Daniel; Leibbrandt, Andreas; de Simoes, Ricardo Matos; Gruber, Susanne; Puc, Urszula; Ebersberger, Ingo; Zoranovic, Tamara; Neely, Gregory G; von Haeseler, Arndt; Ferrandon, Dominique; Penninger, Josef M Genome-wide RNAi screen identifies genes involved in intestinal pathogenic bacterial infection Article de journal Science, 325 (5938), p. 340–343, 2009, ISSN: 1095-9203. Résumé | Liens | BibTeX | Étiquettes: *Genome, *RNA Interference, Animal, Animals, Cell Proliferation, Drosophila melanogaster/*genetics/immunology/*microbiology, Drosophila Proteins/genetics/metabolism, Epithelial Cells, Epithelial Cells/cytology/physiology, ferrandon, Genetically Modified, Genome, Hemocytes, Hemocytes/immunology/metabolism/microbiology, Homeostasis, Immunity, Innate, Innate/*genetics, Insect, Intestinal Mucosa, Intestinal Mucosa/cytology/immunology/metabolism/microbiology, Janus Kinases, Janus Kinases/genetics/metabolism, M3i, Models, RNA Interference, Serratia Infections, Serratia Infections/genetics/*immunology/microbiology, Serratia marcescens, Serratia marcescens/*immunology/physiology, Signal Transduction, STAT Transcription Factors, STAT Transcription Factors/genetics/metabolism, Stem Cells, Stem Cells/cytology/physiology @article{cronin_genome-wide_2009b, title = {Genome-wide RNAi screen identifies genes involved in intestinal pathogenic bacterial infection}, author = {Shane J F Cronin and Nadine T Nehme and Stefanie Limmer and Samuel Liegeois and Andrew J Pospisilik and Daniel Schramek and Andreas Leibbrandt and Ricardo Matos de Simoes and Susanne Gruber and Urszula Puc and Ingo Ebersberger and Tamara Zoranovic and Gregory G Neely and Arndt von Haeseler and Dominique Ferrandon and Josef M Penninger}, doi = {10.1126/science.1173164}, issn = {1095-9203}, year = {2009}, date = {2009-01-01}, journal = {Science}, volume = {325}, number = {5938}, pages = {340--343}, abstract = {Innate immunity represents the first line of defense in animals. We report a genome-wide in vivo Drosophila RNA interference screen to uncover genes involved in susceptibility or resistance to intestinal infection with the bacterium Serratia marcescens. We first employed whole-organism gene suppression, followed by tissue-specific silencing in gut epithelium or hemocytes to identify several hundred genes involved in intestinal antibacterial immunity. Among the pathways identified, we showed that the JAK-STAT signaling pathway controls host defense in the gut by regulating stem cell proliferation and thus epithelial cell homeostasis. Therefore, we revealed multiple genes involved in antibacterial defense and the regulation of innate immunity.}, keywords = {*Genome, *RNA Interference, Animal, Animals, Cell Proliferation, Drosophila melanogaster/*genetics/immunology/*microbiology, Drosophila Proteins/genetics/metabolism, Epithelial Cells, Epithelial Cells/cytology/physiology, ferrandon, Genetically Modified, Genome, Hemocytes, Hemocytes/immunology/metabolism/microbiology, Homeostasis, Immunity, Innate, Innate/*genetics, Insect, Intestinal Mucosa, Intestinal Mucosa/cytology/immunology/metabolism/microbiology, Janus Kinases, Janus Kinases/genetics/metabolism, M3i, Models, RNA Interference, Serratia Infections, Serratia Infections/genetics/*immunology/microbiology, Serratia marcescens, Serratia marcescens/*immunology/physiology, Signal Transduction, STAT Transcription Factors, STAT Transcription Factors/genetics/metabolism, Stem Cells, Stem Cells/cytology/physiology}, pubstate = {published}, tppubtype = {article} } Innate immunity represents the first line of defense in animals. We report a genome-wide in vivo Drosophila RNA interference screen to uncover genes involved in susceptibility or resistance to intestinal infection with the bacterium Serratia marcescens. We first employed whole-organism gene suppression, followed by tissue-specific silencing in gut epithelium or hemocytes to identify several hundred genes involved in intestinal antibacterial immunity. Among the pathways identified, we showed that the JAK-STAT signaling pathway controls host defense in the gut by regulating stem cell proliferation and thus epithelial cell homeostasis. Therefore, we revealed multiple genes involved in antibacterial defense and the regulation of innate immunity. |
2008 |
Goto, Akira; Matsushita, Kazufumi; Gesellchen, Viola; Chamy, Laure El; Kuttenkeuler, David; Takeuchi, Osamu; Hoffmann, Jules A; Akira, Shizuo; Boutros, Michael; Reichhart, Jean-Marc Akirins are highly conserved nuclear proteins required for NF-kappaB-dependent gene expression in drosophila and mice Article de journal Nat. Immunol., 9 (1), p. 97–104, 2008, ISSN: 1529-2916. Résumé | Liens | BibTeX | Étiquettes: Animals, Cell Line, Embryo, Fibroblasts, hoffmann, Humans, Immunity, Innate, Interleukin-1beta, M3i, Mammalian, Mice, NF-kappa B, Nuclear Proteins, Proteins, reichhart, Signal Transduction, Toll-Like Receptors, transgenic, Tumor Necrosis Factor-alpha @article{goto_akirins_2008, title = {Akirins are highly conserved nuclear proteins required for NF-kappaB-dependent gene expression in drosophila and mice}, author = {Akira Goto and Kazufumi Matsushita and Viola Gesellchen and Laure El Chamy and David Kuttenkeuler and Osamu Takeuchi and Jules A Hoffmann and Shizuo Akira and Michael Boutros and Jean-Marc Reichhart}, doi = {10.1038/ni1543}, issn = {1529-2916}, year = {2008}, date = {2008-01-01}, journal = {Nat. Immunol.}, volume = {9}, number = {1}, pages = {97--104}, abstract = {During a genome-wide screen with RNA-mediated interference, we isolated CG8580 as a gene involved in the innate immune response of Drosophila melanogaster. CG8580, which we called Akirin, encoded a protein that acted in parallel with the NF-kappaB transcription factor downstream of the Imd pathway and was required for defense against Gram-negative bacteria. Akirin is highly conserved, and the human genome contains two homologs, one of which was able to rescue the loss-of-function phenotype in drosophila cells. Akirins were strictly localized to the nucleus. Knockout of both Akirin homologs in mice showed that one had an essential function downstream of the Toll-like receptor, tumor necrosis factor and interleukin (IL)-1beta signaling pathways leading to the production of IL-6. Thus, Akirin is a conserved nuclear factor required for innate immune responses.}, keywords = {Animals, Cell Line, Embryo, Fibroblasts, hoffmann, Humans, Immunity, Innate, Interleukin-1beta, M3i, Mammalian, Mice, NF-kappa B, Nuclear Proteins, Proteins, reichhart, Signal Transduction, Toll-Like Receptors, transgenic, Tumor Necrosis Factor-alpha}, pubstate = {published}, tppubtype = {article} } During a genome-wide screen with RNA-mediated interference, we isolated CG8580 as a gene involved in the innate immune response of Drosophila melanogaster. CG8580, which we called Akirin, encoded a protein that acted in parallel with the NF-kappaB transcription factor downstream of the Imd pathway and was required for defense against Gram-negative bacteria. Akirin is highly conserved, and the human genome contains two homologs, one of which was able to rescue the loss-of-function phenotype in drosophila cells. Akirins were strictly localized to the nucleus. Knockout of both Akirin homologs in mice showed that one had an essential function downstream of the Toll-like receptor, tumor necrosis factor and interleukin (IL)-1beta signaling pathways leading to the production of IL-6. Thus, Akirin is a conserved nuclear factor required for innate immune responses. |
Huszar, Tünde; Imler, Jean-Luc Drosophila viruses and the study of antiviral host-defense Article de journal Advances in Virus Research, 72 , p. 227–265, 2008, ISSN: 0065-3527. Résumé | Liens | BibTeX | Étiquettes: Animals, Host-Pathogen Interactions, imler, Immunity, Innate, Insect Viruses, M3i, RNA Interference, RNA Viruses @article{huszar_drosophila_2008, title = {Drosophila viruses and the study of antiviral host-defense}, author = {Tünde Huszar and Jean-Luc Imler}, doi = {10.1016/S0065-3527(08)00406-5}, issn = {0065-3527}, year = {2008}, date = {2008-01-01}, journal = {Advances in Virus Research}, volume = {72}, pages = {227--265}, abstract = {The fruit fly Drosophila melanogaster is a powerful model to study host-pathogen interactions. Most studies so far have focused on extracellular pathogens such as bacteria and fungi. More recently, viruses have come to the front, and RNA interference was shown to play a critical role in the control of viral infections in drosophila. We review here our current knowledge on drosophila viruses. A diverse set of RNA viruses belonging to several families (Rhabdoviridae, Dicistroviridae, Birnaviridae, Reoviridae, Errantiviridae) has been reported in D. melanogaster. By contrast, no DNA virus has been recovered up to now. The drosophila viruses represent powerful tools to study virus-cell interactions in vivo. Analysis of the literature however reveals that for many of them, important gaps exist in our understanding of their replication cycle, genome organization, morphology or pathogenesis. The data obtained in the past few years on antiviral defense mechanisms in drosophila, which point to evolutionary conserved pathways, highlight the potential of the D. melanogaster model to study antiviral innate immunity and to better understand the complex interaction between arthropod-borne viruses and their insect vectors.}, keywords = {Animals, Host-Pathogen Interactions, imler, Immunity, Innate, Insect Viruses, M3i, RNA Interference, RNA Viruses}, pubstate = {published}, tppubtype = {article} } The fruit fly Drosophila melanogaster is a powerful model to study host-pathogen interactions. Most studies so far have focused on extracellular pathogens such as bacteria and fungi. More recently, viruses have come to the front, and RNA interference was shown to play a critical role in the control of viral infections in drosophila. We review here our current knowledge on drosophila viruses. A diverse set of RNA viruses belonging to several families (Rhabdoviridae, Dicistroviridae, Birnaviridae, Reoviridae, Errantiviridae) has been reported in D. melanogaster. By contrast, no DNA virus has been recovered up to now. The drosophila viruses represent powerful tools to study virus-cell interactions in vivo. Analysis of the literature however reveals that for many of them, important gaps exist in our understanding of their replication cycle, genome organization, morphology or pathogenesis. The data obtained in the past few years on antiviral defense mechanisms in drosophila, which point to evolutionary conserved pathways, highlight the potential of the D. melanogaster model to study antiviral innate immunity and to better understand the complex interaction between arthropod-borne viruses and their insect vectors. |
2007 |
Ferrandon, Dominique; Imler, Jean-Luc; Hetru, Charles; Hoffmann, Jules A The Drosophila systemic immune response: sensing and signalling during bacterial and fungal infections Article de journal Nat Rev Immunol, 7 , p. 862–74, 2007. Résumé | BibTeX | Étiquettes: Animals, Bacterial Infections/*immunology/microbiology, Drosophila melanogaster/genetics/*immunology/microbiology, ferrandon, hoffmann, imler, Immunity, M3i, Mycoses/*immunology/microbiology, Natural/genetics, Signal Transduction/genetics/*immunology @article{ferrandon_drosophila_2007b, title = {The Drosophila systemic immune response: sensing and signalling during bacterial and fungal infections}, author = {Dominique Ferrandon and Jean-Luc Imler and Charles Hetru and Jules A Hoffmann}, year = {2007}, date = {2007-11-01}, journal = {Nat Rev Immunol}, volume = {7}, pages = {862--74}, abstract = {A hallmark of the potent, multifaceted antimicrobial defence of Drosophila melanogaster is the challenge-induced synthesis of several families of antimicrobial peptides by cells in the fat body. The basic mechanisms of recognition of various types of microbial infections by the adult fly are now understood, often in great detail. We have further gained valuable insight into the infection-induced gene reprogramming by nuclear factor-kappaB (NF-kappaB) family members under the dependence of complex intracellular signalling cascades. The striking parallels between the adult fly response and mammalian innate immune defences described below point to a common ancestry and validate the relevance of the fly defence as a paradigm for innate immunity.}, keywords = {Animals, Bacterial Infections/*immunology/microbiology, Drosophila melanogaster/genetics/*immunology/microbiology, ferrandon, hoffmann, imler, Immunity, M3i, Mycoses/*immunology/microbiology, Natural/genetics, Signal Transduction/genetics/*immunology}, pubstate = {published}, tppubtype = {article} } A hallmark of the potent, multifaceted antimicrobial defence of Drosophila melanogaster is the challenge-induced synthesis of several families of antimicrobial peptides by cells in the fat body. The basic mechanisms of recognition of various types of microbial infections by the adult fly are now understood, often in great detail. We have further gained valuable insight into the infection-induced gene reprogramming by nuclear factor-kappaB (NF-kappaB) family members under the dependence of complex intracellular signalling cascades. The striking parallels between the adult fly response and mammalian innate immune defences described below point to a common ancestry and validate the relevance of the fly defence as a paradigm for innate immunity. |
Beutler, Bruce; Eidenschenk, Celine; Crozat, Karine; Imler, Jean-Luc; Takeuchi, Osamu; Hoffmann, Jules A; Akira, Shizuo Genetic analysis of resistance to viral infection Article de journal Nature Reviews. Immunology, 7 (10), p. 753–766, 2007, ISSN: 1474-1741. Résumé | Liens | BibTeX | Étiquettes: Animals, Antiviral Agents, Disease Susceptibility, Drug Resistance, Eukaryotic Cells, hoffmann, Humans, imler, Immunity, M3i, Mutation, Viral, Virus Diseases, viruses @article{beutler_genetic_2007, title = {Genetic analysis of resistance to viral infection}, author = {Bruce Beutler and Celine Eidenschenk and Karine Crozat and Jean-Luc Imler and Osamu Takeuchi and Jules A Hoffmann and Shizuo Akira}, doi = {10.1038/nri2174}, issn = {1474-1741}, year = {2007}, date = {2007-10-01}, journal = {Nature Reviews. Immunology}, volume = {7}, number = {10}, pages = {753--766}, abstract = {As machines that reprogramme eukaryotic cells to suit their own purposes, viruses present a difficult problem for multicellular hosts, and indeed, have become one of the central pre-occupations of the immune system. Unable to permanently outpace individual viruses in an evolutionary footrace, higher eukaryotes have evolved broadly active mechanisms with which to sense viruses and suppress their proliferation. These mechanisms have recently been elucidated by a combination of forward and reverse genetic methods. Some of these mechanisms are clearly ancient, whereas others are relatively new. All are remarkably adept at discriminating self from non-self, and allow the host to cope with what might seem an impossible predicament.}, keywords = {Animals, Antiviral Agents, Disease Susceptibility, Drug Resistance, Eukaryotic Cells, hoffmann, Humans, imler, Immunity, M3i, Mutation, Viral, Virus Diseases, viruses}, pubstate = {published}, tppubtype = {article} } As machines that reprogramme eukaryotic cells to suit their own purposes, viruses present a difficult problem for multicellular hosts, and indeed, have become one of the central pre-occupations of the immune system. Unable to permanently outpace individual viruses in an evolutionary footrace, higher eukaryotes have evolved broadly active mechanisms with which to sense viruses and suppress their proliferation. These mechanisms have recently been elucidated by a combination of forward and reverse genetic methods. Some of these mechanisms are clearly ancient, whereas others are relatively new. All are remarkably adept at discriminating self from non-self, and allow the host to cope with what might seem an impossible predicament. |
2006 |
Gottar, Marie; Gobert, Vanessa; Matskevich, Alexey A; Reichhart, Jean-Marc; Wang, Chengshu; Butt, Tariq M; Belvin, Marcia; Hoffmann, Jules A; Ferrandon, Dominique Dual detection of fungal infections in Drosophila via recognition of glucans and sensing of virulence factors Article de journal Cell, 127 (7), p. 1425–1437, 2006, ISSN: 0092-8674. Résumé | Liens | BibTeX | Étiquettes: Animals, Antibody Formation, Beauveria, Candida albicans, Carrier Proteins, Cellular, ferrandon, Glucans, hoffmann, Immunity, Immunological, M3i, Metarhizium, Models, Polysaccharides, reichhart, Serine Endopeptidases, Signal Transduction, Virulence Factors @article{gottar_dual_2006, title = {Dual detection of fungal infections in Drosophila via recognition of glucans and sensing of virulence factors}, author = {Marie Gottar and Vanessa Gobert and Alexey A Matskevich and Jean-Marc Reichhart and Chengshu Wang and Tariq M Butt and Marcia Belvin and Jules A Hoffmann and Dominique Ferrandon}, doi = {10.1016/j.cell.2006.10.046}, issn = {0092-8674}, year = {2006}, date = {2006-12-01}, journal = {Cell}, volume = {127}, number = {7}, pages = {1425--1437}, abstract = {The Drosophila immune system discriminates between various types of infections and activates appropriate signal transduction pathways to combat the invading microorganisms. The Toll pathway is required for the host response against fungal and most Gram-positive bacterial infections. The sensing of Gram-positive bacteria is mediated by the pattern recognition receptors PGRP-SA and GNBP1 that cooperate to detect the presence of infections in the host. Here, we report that GNBP3 is a pattern recognition receptor that is required for the detection of fungal cell wall components. Strikingly, we find that there is a second, parallel pathway acting jointly with GNBP3. The Drosophila Persephone protease activates the Toll pathway when proteolytically matured by the secreted fungal virulence factor PR1. Thus, the detection of fungal infections in Drosophila relies both on the recognition of invariant microbial patterns and on monitoring the effects of virulence factors on the host.}, keywords = {Animals, Antibody Formation, Beauveria, Candida albicans, Carrier Proteins, Cellular, ferrandon, Glucans, hoffmann, Immunity, Immunological, M3i, Metarhizium, Models, Polysaccharides, reichhart, Serine Endopeptidases, Signal Transduction, Virulence Factors}, pubstate = {published}, tppubtype = {article} } The Drosophila immune system discriminates between various types of infections and activates appropriate signal transduction pathways to combat the invading microorganisms. The Toll pathway is required for the host response against fungal and most Gram-positive bacterial infections. The sensing of Gram-positive bacteria is mediated by the pattern recognition receptors PGRP-SA and GNBP1 that cooperate to detect the presence of infections in the host. Here, we report that GNBP3 is a pattern recognition receptor that is required for the detection of fungal cell wall components. Strikingly, we find that there is a second, parallel pathway acting jointly with GNBP3. The Drosophila Persephone protease activates the Toll pathway when proteolytically matured by the secreted fungal virulence factor PR1. Thus, the detection of fungal infections in Drosophila relies both on the recognition of invariant microbial patterns and on monitoring the effects of virulence factors on the host. |
Shiao, Shin-Hong; Whitten, Miranda M A; Zachary, Daniel; Hoffmann, Jules A; Levashina, Elena A Fz2 and cdc42 mediate melanization and actin polymerization but are dispensable for Plasmodium killing in the mosquito midgut Article de journal PLoS Pathog., 2 (12), p. e133, 2006, ISSN: 1553-7374. Résumé | Liens | BibTeX | Étiquettes: Actins, Animals, Anopheles, Carrier Proteins, cdc42 GTP-Binding Protein, Double-Stranded, Electron, Frizzled Receptors, Gastrointestinal Tract, hoffmann, Host-Parasite Interactions, Immunity, Innate, Insect Vectors, Intestinal Mucosa, M3i, Melanins, Microarray Analysis, Microscopy, Plasmodium berghei, Polymers, Protozoan, RNA, scanning, telomerase @article{shiao_fz2_2006, title = {Fz2 and cdc42 mediate melanization and actin polymerization but are dispensable for Plasmodium killing in the mosquito midgut}, author = {Shin-Hong Shiao and Miranda M A Whitten and Daniel Zachary and Jules A Hoffmann and Elena A Levashina}, doi = {10.1371/journal.ppat.0020133}, issn = {1553-7374}, year = {2006}, date = {2006-12-01}, journal = {PLoS Pathog.}, volume = {2}, number = {12}, pages = {e133}, abstract = {The midgut epithelium of the mosquito malaria vector Anopheles is a hostile environment for Plasmodium, with most parasites succumbing to host defenses. This study addresses morphological and ultrastructural features associated with Plasmodium berghei ookinete invasion in Anopheles gambiae midguts to define the sites and possible mechanisms of parasite killing. We show by transmission electron microscopy and immunofluorescence that the majority of ookinetes are killed in the extracellular space. Dead or dying ookinetes are surrounded by a polymerized actin zone formed within the basal cytoplasm of adjacent host epithelial cells. In refractory strain mosquitoes, we found that formation of this zone is strongly linked to prophenoloxidase activation leading to melanization. Furthermore, we identify two factors controlling both phenomena: the transmembrane receptor frizzled-2 and the guanosine triphosphate-binding protein cell division cycle 42. However, the disruption of actin polymerization and melanization by double-stranded RNA inhibition did not affect ookinete survival. Our results separate the mechanisms of parasite killing from subsequent reactions manifested by actin polymerization and prophenoloxidase activation in the A. gambiae-P. berghei model. These latter processes are reminiscent of wound healing in other organisms, and we propose that they represent a form of wound-healing response directed towards a moribund ookinete, which is perceived as damaged tissue.}, keywords = {Actins, Animals, Anopheles, Carrier Proteins, cdc42 GTP-Binding Protein, Double-Stranded, Electron, Frizzled Receptors, Gastrointestinal Tract, hoffmann, Host-Parasite Interactions, Immunity, Innate, Insect Vectors, Intestinal Mucosa, M3i, Melanins, Microarray Analysis, Microscopy, Plasmodium berghei, Polymers, Protozoan, RNA, scanning, telomerase}, pubstate = {published}, tppubtype = {article} } The midgut epithelium of the mosquito malaria vector Anopheles is a hostile environment for Plasmodium, with most parasites succumbing to host defenses. This study addresses morphological and ultrastructural features associated with Plasmodium berghei ookinete invasion in Anopheles gambiae midguts to define the sites and possible mechanisms of parasite killing. We show by transmission electron microscopy and immunofluorescence that the majority of ookinetes are killed in the extracellular space. Dead or dying ookinetes are surrounded by a polymerized actin zone formed within the basal cytoplasm of adjacent host epithelial cells. In refractory strain mosquitoes, we found that formation of this zone is strongly linked to prophenoloxidase activation leading to melanization. Furthermore, we identify two factors controlling both phenomena: the transmembrane receptor frizzled-2 and the guanosine triphosphate-binding protein cell division cycle 42. However, the disruption of actin polymerization and melanization by double-stranded RNA inhibition did not affect ookinete survival. Our results separate the mechanisms of parasite killing from subsequent reactions manifested by actin polymerization and prophenoloxidase activation in the A. gambiae-P. berghei model. These latter processes are reminiscent of wound healing in other organisms, and we propose that they represent a form of wound-healing response directed towards a moribund ookinete, which is perceived as damaged tissue. |
Frolet, Cécile; Thoma, Martine; Blandin, Stéphanie A; Hoffmann, Jules A; Levashina, Elena A Boosting NF-kappaB-dependent basal immunity of Anopheles gambiae aborts development of Plasmodium berghei Article de journal Immunity, 25 (4), p. 677–685, 2006, ISSN: 1074-7613. Résumé | Liens | BibTeX | Étiquettes: Animals, Anopheles gambiae, blandin, Gene Expression, Gene Expression Regulation, Genes, hoffmann, Immunity, Insect, M3i, NF-kappa B, Plasmodium berghei, telomerase @article{frolet_boosting_2006, title = {Boosting NF-kappaB-dependent basal immunity of Anopheles gambiae aborts development of Plasmodium berghei}, author = {Cécile Frolet and Martine Thoma and Stéphanie A Blandin and Jules A Hoffmann and Elena A Levashina}, url = {http://www.ncbi.nlm.nih.gov/pubmed/17045818}, doi = {10.1016/j.immuni.2006.08.019}, issn = {1074-7613}, year = {2006}, date = {2006-10-01}, journal = {Immunity}, volume = {25}, number = {4}, pages = {677--685}, abstract = {Anopheles gambiae, the major vector for the protozoan malaria parasite Plasmodium falciparum, mounts powerful antiparasitic responses that cause marked parasite loss during midgut invasion. Here, we showed that these antiparasitic defenses were composed of pre- and postinvasion phases and that the preinvasion phase was predominantly regulated by Rel1 and Rel2 members of the NF-kappaB transcription factors. Concurrent silencing of Rel1 and Rel2 decreased the basal expression of the major antiparasitic genes TEP1 and LRIM1 and abolished resistance of Anopheles to the rodent malaria parasite P. berghei. Conversely, depletion of a negative regulator of Rel1, Cactus, prior to infection, enhanced the basal expression of TEP1 and of other immune factors and completely prevented parasite development. Our findings uncover the crucial role of the preinvasion defense in the elimination of parasites, which is at least in part based on circulating blood molecules.}, keywords = {Animals, Anopheles gambiae, blandin, Gene Expression, Gene Expression Regulation, Genes, hoffmann, Immunity, Insect, M3i, NF-kappa B, Plasmodium berghei, telomerase}, pubstate = {published}, tppubtype = {article} } Anopheles gambiae, the major vector for the protozoan malaria parasite Plasmodium falciparum, mounts powerful antiparasitic responses that cause marked parasite loss during midgut invasion. Here, we showed that these antiparasitic defenses were composed of pre- and postinvasion phases and that the preinvasion phase was predominantly regulated by Rel1 and Rel2 members of the NF-kappaB transcription factors. Concurrent silencing of Rel1 and Rel2 decreased the basal expression of the major antiparasitic genes TEP1 and LRIM1 and abolished resistance of Anopheles to the rodent malaria parasite P. berghei. Conversely, depletion of a negative regulator of Rel1, Cactus, prior to infection, enhanced the basal expression of TEP1 and of other immune factors and completely prevented parasite development. Our findings uncover the crucial role of the preinvasion defense in the elimination of parasites, which is at least in part based on circulating blood molecules. |
Evans, J D; Aronstein, K; Chen, Y P; Hetru, Charles; Imler, Jean-Luc; Jiang, H; Kanost, M; Thompson, G J; Zou, Z; Hultmark, D Immune pathways and defence mechanisms in honey bees Apis mellifera Article de journal Insect Molecular Biology, 15 (5), p. 645–656, 2006, ISSN: 0962-1075. Résumé | Liens | BibTeX | Étiquettes: Animals, Bees, Carrier Proteins, Genome, imler, Immunity, Insect, Janus Kinases, M3i, Multigene Family, Serine Endopeptidases, Signal Transduction, STAT Transcription Factors, Toll-Like Receptors @article{evans_immune_2006, title = {Immune pathways and defence mechanisms in honey bees Apis mellifera}, author = {J D Evans and K Aronstein and Y P Chen and Charles Hetru and Jean-Luc Imler and H Jiang and M Kanost and G J Thompson and Z Zou and D Hultmark}, doi = {10.1111/j.1365-2583.2006.00682.x}, issn = {0962-1075}, year = {2006}, date = {2006-10-01}, journal = {Insect Molecular Biology}, volume = {15}, number = {5}, pages = {645--656}, abstract = {Social insects are able to mount both group-level and individual defences against pathogens. Here we focus on individual defences, by presenting a genome-wide analysis of immunity in a social insect, the honey bee Apis mellifera. We present honey bee models for each of four signalling pathways associated with immunity, identifying plausible orthologues for nearly all predicted pathway members. When compared to the sequenced Drosophila and Anopheles genomes, honey bees possess roughly one-third as many genes in 17 gene families implicated in insect immunity. We suggest that an implied reduction in immune flexibility in bees reflects either the strength of social barriers to disease, or a tendency for bees to be attacked by a limited set of highly coevolved pathogens.}, keywords = {Animals, Bees, Carrier Proteins, Genome, imler, Immunity, Insect, Janus Kinases, M3i, Multigene Family, Serine Endopeptidases, Signal Transduction, STAT Transcription Factors, Toll-Like Receptors}, pubstate = {published}, tppubtype = {article} } Social insects are able to mount both group-level and individual defences against pathogens. Here we focus on individual defences, by presenting a genome-wide analysis of immunity in a social insect, the honey bee Apis mellifera. We present honey bee models for each of four signalling pathways associated with immunity, identifying plausible orthologues for nearly all predicted pathway members. When compared to the sequenced Drosophila and Anopheles genomes, honey bees possess roughly one-third as many genes in 17 gene families implicated in insect immunity. We suggest that an implied reduction in immune flexibility in bees reflects either the strength of social barriers to disease, or a tendency for bees to be attacked by a limited set of highly coevolved pathogens. |
Chen, Li-Ying; Wang, Juinn-Chin; Hyvert, Yann; Lin, Hui-Ping; Perrimon, Norbert; Imler, Jean-Luc; Hsu, Jui-Chou Weckle is a zinc finger adaptor of the toll pathway in dorsoventral patterning of the Drosophila embryo Article de journal Current biology: CB, 16 (12), p. 1183–1193, 2006, ISSN: 0960-9822. Résumé | Liens | BibTeX | Étiquettes: Adaptor Proteins, Animals, Antigens, Biological, Body Patterning, Cell Membrane, Differentiation, dimerization, DNA-Binding Proteins, Embryo, Epistasis, Genetic, imler, Immunity, Immunologic, Innate, M3i, Models, Mutation, Nonmammalian, Phenotype, Phosphoproteins, Receptors, Signal Transducing, Toll-Like Receptors, Transcription Factors, Zinc Fingers @article{chen_weckle_2006, title = {Weckle is a zinc finger adaptor of the toll pathway in dorsoventral patterning of the Drosophila embryo}, author = {Li-Ying Chen and Juinn-Chin Wang and Yann Hyvert and Hui-Ping Lin and Norbert Perrimon and Jean-Luc Imler and Jui-Chou Hsu}, doi = {10.1016/j.cub.2006.05.050}, issn = {0960-9822}, year = {2006}, date = {2006-06-01}, journal = {Current biology: CB}, volume = {16}, number = {12}, pages = {1183--1193}, abstract = {BACKGROUND: The Drosophila Toll pathway takes part in both establishment of the embryonic dorsoventral axis and induction of the innate immune response in adults. Upon activation by the cytokine Spätzle, Toll interacts with the adaptor proteins DmMyD88 and Tube and the kinase Pelle and triggers degradation of the inhibitor Cactus, thus allowing the nuclear translocation of the transcription factor Dorsal/Dif. weckle (wek) was previously identified as a new dorsal group gene that encodes a putative zinc finger transcription factor. However, its role in the Toll pathway was unknown. RESULTS: Here, we isolated new wek alleles and demonstrated that cactus is epistatic to wek, which in turn is epistatic to Toll. Consistent with this, Wek localizes to the plasma membrane of embryos, independently of Toll signaling. Wek homodimerizes and associates with Toll. Moreover, Wek binds to and localizes DmMyD88 to the plasma membrane. Thus, Wek acts as an adaptor to assemble/stabilize a Toll/Wek/DmMyD88/Tube complex. Remarkably, unlike the DmMyD88/tube/pelle/cactus gene cassette of the Toll pathway, wek plays a minimal role, if any, in the immune defense against Gram-positive bacteria and fungi. CONCLUSIONS: We conclude that Wek is an adaptor to link Toll and DmMyD88 and is required for efficient recruitment of DmMyD88 to Toll. Unexpectedly, wek is dispensable for innate immune response, thus revealing differences in the Toll-mediated activation of Dorsal in the embryo and Dif in the fat body of adult flies.}, keywords = {Adaptor Proteins, Animals, Antigens, Biological, Body Patterning, Cell Membrane, Differentiation, dimerization, DNA-Binding Proteins, Embryo, Epistasis, Genetic, imler, Immunity, Immunologic, Innate, M3i, Models, Mutation, Nonmammalian, Phenotype, Phosphoproteins, Receptors, Signal Transducing, Toll-Like Receptors, Transcription Factors, Zinc Fingers}, pubstate = {published}, tppubtype = {article} } BACKGROUND: The Drosophila Toll pathway takes part in both establishment of the embryonic dorsoventral axis and induction of the innate immune response in adults. Upon activation by the cytokine Spätzle, Toll interacts with the adaptor proteins DmMyD88 and Tube and the kinase Pelle and triggers degradation of the inhibitor Cactus, thus allowing the nuclear translocation of the transcription factor Dorsal/Dif. weckle (wek) was previously identified as a new dorsal group gene that encodes a putative zinc finger transcription factor. However, its role in the Toll pathway was unknown. RESULTS: Here, we isolated new wek alleles and demonstrated that cactus is epistatic to wek, which in turn is epistatic to Toll. Consistent with this, Wek localizes to the plasma membrane of embryos, independently of Toll signaling. Wek homodimerizes and associates with Toll. Moreover, Wek binds to and localizes DmMyD88 to the plasma membrane. Thus, Wek acts as an adaptor to assemble/stabilize a Toll/Wek/DmMyD88/Tube complex. Remarkably, unlike the DmMyD88/tube/pelle/cactus gene cassette of the Toll pathway, wek plays a minimal role, if any, in the immune defense against Gram-positive bacteria and fungi. CONCLUSIONS: We conclude that Wek is an adaptor to link Toll and DmMyD88 and is required for efficient recruitment of DmMyD88 to Toll. Unexpectedly, wek is dispensable for innate immune response, thus revealing differences in the Toll-mediated activation of Dorsal in the embryo and Dif in the fat body of adult flies. |
Leclerc, Vincent; Pelte, Nadège; Chamy, Laure El; Martinelli, Cosimo; Ligoxygakis, Petros; Hoffmann, Jules A; Reichhart, Jean-Marc Prophenoloxidase activation is not required for survival to microbial infections in Drosophila Article de journal EMBO Rep., 7 (2), p. 231–235, 2006, ISSN: 1469-221X. Résumé | Liens | BibTeX | Étiquettes: Animals, Bacterial Infections, Catechol Oxidase, Enzyme Activation, Enzyme Precursors, Gram-Negative Bacteria, Gram-Positive Bacteria, Hemolymph, hoffmann, Immunity, Innate, M3i, Mutation, reichhart, Survival Rate @article{leclerc_prophenoloxidase_2006, title = {Prophenoloxidase activation is not required for survival to microbial infections in Drosophila}, author = {Vincent Leclerc and Nadège Pelte and Laure El Chamy and Cosimo Martinelli and Petros Ligoxygakis and Jules A Hoffmann and Jean-Marc Reichhart}, doi = {10.1038/sj.embor.7400592}, issn = {1469-221X}, year = {2006}, date = {2006-02-01}, journal = {EMBO Rep.}, volume = {7}, number = {2}, pages = {231--235}, abstract = {The antimicrobial defence of Drosophila relies on cellular and humoral processes, of which the inducible synthesis of antimicrobial peptides has attracted interest in recent years. Another potential line of defence is the activation, by a proteolytic cascade, of phenoloxidase, which leads to the production of quinones and melanin. However, in spite of several publications on this subject, the contribution of phenoloxidase activation to resistance to infections has not been established under appropriate in vivo conditions. Here, we have isolated the first Drosophila mutant for a prophenoloxidase-activating enzyme (PAE1). In contrast to wild-type flies, PAE1 mutants fail to activate phenoloxidase in the haemolymph following microbial challenge. Surprisingly, we find that these mutants are as resistant to infections as wild-type flies, in the total absence of circulating phenoloxidase activity. This raises the question with regard to the precise function of phenoloxidase activation in defence, if any.}, keywords = {Animals, Bacterial Infections, Catechol Oxidase, Enzyme Activation, Enzyme Precursors, Gram-Negative Bacteria, Gram-Positive Bacteria, Hemolymph, hoffmann, Immunity, Innate, M3i, Mutation, reichhart, Survival Rate}, pubstate = {published}, tppubtype = {article} } The antimicrobial defence of Drosophila relies on cellular and humoral processes, of which the inducible synthesis of antimicrobial peptides has attracted interest in recent years. Another potential line of defence is the activation, by a proteolytic cascade, of phenoloxidase, which leads to the production of quinones and melanin. However, in spite of several publications on this subject, the contribution of phenoloxidase activation to resistance to infections has not been established under appropriate in vivo conditions. Here, we have isolated the first Drosophila mutant for a prophenoloxidase-activating enzyme (PAE1). In contrast to wild-type flies, PAE1 mutants fail to activate phenoloxidase in the haemolymph following microbial challenge. Surprisingly, we find that these mutants are as resistant to infections as wild-type flies, in the total absence of circulating phenoloxidase activity. This raises the question with regard to the precise function of phenoloxidase activation in defence, if any. |
Galiana-Arnoux, Delphine; Imler, Jean-Luc Toll-like receptors and innate antiviral immunity Article de journal Tissue Antigens, 67 (4), p. 267–276, 2006, ISSN: 0001-2815. Résumé | Liens | BibTeX | Étiquettes: Animals, Humans, imler, Immunity, Innate, M3i, Signal Transduction, Toll-Like Receptors, Virus Diseases @article{galiana-arnoux_toll-like_2006, title = {Toll-like receptors and innate antiviral immunity}, author = {Delphine Galiana-Arnoux and Jean-Luc Imler}, doi = {10.1111/j.1399-0039.2006.00583.x}, issn = {0001-2815}, year = {2006}, date = {2006-01-01}, journal = {Tissue Antigens}, volume = {67}, number = {4}, pages = {267--276}, abstract = {Viral infections are first detected by a set of innate immunity receptors that detect primary infections by pathogens, and trigger a transcriptional response. Among the induced target genes, type I interferons (IFNs) are central to the antiviral response of the host. The receptors and signaling pathways that mediate the strong induction of the synthesis of these cytokines have long remained elusive. In the past few years, Toll-like receptors (TLRs) emerged as important sensors of infections. Several TLRs participate in the recognition of virus infection, interacting in particular with viral nucleic acids. Upon activation, TLRs interact with different cytosolic adapter molecules and activate transcription factors of the nuclear factor-kappaB and IFN regulatory factor families that concur to mediate induction of IFN-alpha/beta and other inflammatory cytokines. In addition to the transmembrane TLRs, cytosolic helicases also detect viral nucleic acids, and trigger type I IFN synthesis.}, keywords = {Animals, Humans, imler, Immunity, Innate, M3i, Signal Transduction, Toll-Like Receptors, Virus Diseases}, pubstate = {published}, tppubtype = {article} } Viral infections are first detected by a set of innate immunity receptors that detect primary infections by pathogens, and trigger a transcriptional response. Among the induced target genes, type I interferons (IFNs) are central to the antiviral response of the host. The receptors and signaling pathways that mediate the strong induction of the synthesis of these cytokines have long remained elusive. In the past few years, Toll-like receptors (TLRs) emerged as important sensors of infections. Several TLRs participate in the recognition of virus infection, interacting in particular with viral nucleic acids. Upon activation, TLRs interact with different cytosolic adapter molecules and activate transcription factors of the nuclear factor-kappaB and IFN regulatory factor families that concur to mediate induction of IFN-alpha/beta and other inflammatory cytokines. In addition to the transmembrane TLRs, cytosolic helicases also detect viral nucleic acids, and trigger type I IFN synthesis. |
2005 |
Reichhart, Jean-Marc Tip of another iceberg: Drosophila serpins Article de journal Trends Cell Biol., 15 (12), p. 659–665, 2005, ISSN: 0962-8924. Résumé | Liens | BibTeX | Étiquettes: Animals, Immunity, M3i, Protein Conformation, reichhart, Serine Proteinase Inhibitors, Serpins @article{reichhart_tip_2005, title = {Tip of another iceberg: Drosophila serpins}, author = {Jean-Marc Reichhart}, doi = {10.1016/j.tcb.2005.10.001}, issn = {0962-8924}, year = {2005}, date = {2005-12-01}, journal = {Trends Cell Biol.}, volume = {15}, number = {12}, pages = {659--665}, abstract = {Serpins are serine protease inhibitors with a conserved structure that have been identified in nearly all species and act as suicide substrates by binding covalently to their target proteases. Serpins regulate various physiological processes and defence mechanisms. In humans, several serpin mutations are linked to diseases. The genome of Drosophila melanogaster encodes 29 serpins and even more serine proteases. To date, three serpins have been investigated in detail. Spn27A controls the Toll pathway during early development and is involved in defence reactions in adult flies. SPN42DaA is an inhibitor of furin, a subtilisin-like convertase that is required for pro-protein maturation. Spn43Ac controls the Toll pathway during the immune response. In each case, Drosophila genetics has shed new light on the function of these serine protease inhibitors.}, keywords = {Animals, Immunity, M3i, Protein Conformation, reichhart, Serine Proteinase Inhibitors, Serpins}, pubstate = {published}, tppubtype = {article} } Serpins are serine protease inhibitors with a conserved structure that have been identified in nearly all species and act as suicide substrates by binding covalently to their target proteases. Serpins regulate various physiological processes and defence mechanisms. In humans, several serpin mutations are linked to diseases. The genome of Drosophila melanogaster encodes 29 serpins and even more serine proteases. To date, three serpins have been investigated in detail. Spn27A controls the Toll pathway during early development and is involved in defence reactions in adult flies. SPN42DaA is an inhibitor of furin, a subtilisin-like convertase that is required for pro-protein maturation. Spn43Ac controls the Toll pathway during the immune response. In each case, Drosophila genetics has shed new light on the function of these serine protease inhibitors. |
Royet, Julien; Reichhart, Jean-Marc; Hoffmann, Jules A Sensing and signaling during infection in Drosophila Article de journal Curr. Opin. Immunol., 17 (1), p. 11–17, 2005, ISSN: 0952-7915. Résumé | Liens | BibTeX | Étiquettes: Animals, Antimicrobial Cationic Peptides, Bacterial Infections, Gene Expression Regulation, Genome, hoffmann, Immunity, Innate, M3i, reichhart, Signal Transduction @article{royet_sensing_2005, title = {Sensing and signaling during infection in Drosophila}, author = {Julien Royet and Jean-Marc Reichhart and Jules A Hoffmann}, doi = {10.1016/j.coi.2004.12.002}, issn = {0952-7915}, year = {2005}, date = {2005-02-01}, journal = {Curr. Opin. Immunol.}, volume = {17}, number = {1}, pages = {11--17}, abstract = {Most of the progress in dissecting the Drosophila antimicrobial response over the past decade has centered around intracellular signaling pathways in immune response tissues and expression of genes encoding antimicrobial peptide genes. The past few years, however, have witnessed significant advances in our understanding of the recognition of microbial invaders and subsequent activation of signaling cascades. In particular, the roles of peptidoglycan recognition proteins, which have known homologues in mammals, have been recognized and examined at the structural and functional levels.}, keywords = {Animals, Antimicrobial Cationic Peptides, Bacterial Infections, Gene Expression Regulation, Genome, hoffmann, Immunity, Innate, M3i, reichhart, Signal Transduction}, pubstate = {published}, tppubtype = {article} } Most of the progress in dissecting the Drosophila antimicrobial response over the past decade has centered around intracellular signaling pathways in immune response tissues and expression of genes encoding antimicrobial peptide genes. The past few years, however, have witnessed significant advances in our understanding of the recognition of microbial invaders and subsequent activation of signaling cascades. In particular, the roles of peptidoglycan recognition proteins, which have known homologues in mammals, have been recognized and examined at the structural and functional levels. |
Martinelli, Cosimo; Reichhart, Jean-Marc Evolution and integration of innate immune systems from fruit flies to man: lessons and questions Article de journal J. Endotoxin Res., 11 (4), p. 243–248, 2005, ISSN: 0968-0519. Résumé | Liens | BibTeX | Étiquettes: Animals, Biological Evolution, Cell Surface, Forecasting, Humans, Immunity, Immunological, Innate, M3i, Membrane Glycoproteins, Models, Receptors, reichhart, Signal Transduction, Toll-Like Receptor 5, Toll-Like Receptors @article{martinelli_evolution_2005, title = {Evolution and integration of innate immune systems from fruit flies to man: lessons and questions}, author = {Cosimo Martinelli and Jean-Marc Reichhart}, doi = {10.1179/096805105X37411}, issn = {0968-0519}, year = {2005}, date = {2005-01-01}, journal = {J. Endotoxin Res.}, volume = {11}, number = {4}, pages = {243--248}, abstract = {Despite broad differences in morphology, ecology and behavior, the fruit fly Drosophila melanogaster and humans show a remarkably high degree of conservation for many molecular, cellular, and developmental aspects of their biology. During the last decade, similarities have also been discovered in some of the mechanisms regulating their innate immune system. These parallels regard mainly the Toll-like receptor family and the intracellular signaling pathways involved in the control of the immune response. However, if the overall similarities are important, the detailed pathogen recognition mechanisms differ significantly between fly and humans, highlighting a complicated evolutionary history of the metazoan innate defenses. In this review, we will discuss the main similarities and differences between the two types of organisms. We hope that this current knowledge will be used as a starting point for a more comprehensive view of innate immunity within the broad variety of metazoan phyla.}, keywords = {Animals, Biological Evolution, Cell Surface, Forecasting, Humans, Immunity, Immunological, Innate, M3i, Membrane Glycoproteins, Models, Receptors, reichhart, Signal Transduction, Toll-Like Receptor 5, Toll-Like Receptors}, pubstate = {published}, tppubtype = {article} } Despite broad differences in morphology, ecology and behavior, the fruit fly Drosophila melanogaster and humans show a remarkably high degree of conservation for many molecular, cellular, and developmental aspects of their biology. During the last decade, similarities have also been discovered in some of the mechanisms regulating their innate immune system. These parallels regard mainly the Toll-like receptor family and the intracellular signaling pathways involved in the control of the immune response. However, if the overall similarities are important, the detailed pathogen recognition mechanisms differ significantly between fly and humans, highlighting a complicated evolutionary history of the metazoan innate defenses. In this review, we will discuss the main similarities and differences between the two types of organisms. We hope that this current knowledge will be used as a starting point for a more comprehensive view of innate immunity within the broad variety of metazoan phyla. |
Imler, Jean-Luc; Bulet, Philippe Antimicrobial peptides in Drosophila: structures, activities and gene regulation Article de journal Chemical Immunology and Allergy, 86 , p. 1–21, 2005, ISSN: 1660-2242. Résumé | Liens | BibTeX | Étiquettes: Animals, Antimicrobial Cationic Peptides, Defensins, Gene Expression Regulation, Genes, Glycopeptides, imler, Immunity, Innate, Insect, Insect Proteins, M3i, Molecular Structure, Signal Transduction @article{imler_antimicrobial_2005, title = {Antimicrobial peptides in Drosophila: structures, activities and gene regulation}, author = {Jean-Luc Imler and Philippe Bulet}, doi = {10.1159/000086648}, issn = {1660-2242}, year = {2005}, date = {2005-01-01}, journal = {Chemical Immunology and Allergy}, volume = {86}, pages = {1--21}, abstract = {The production of antimicrobial peptides (AMPs) is an important aspect of host-defence in multicellular organisms. Biochemical analysis of the hemolymph of the fruit-fly Drosophila melanogaster and other Diptera has led to the discovery of eight classes of AMPs. These peptides can be grouped into three families based on their main biological targets, gram-positive bacteria (defensin), gram-negative bacteria (cecropins, drosocin, attacins, diptericin, MPAC), or fungi (drosomycin, metchnikowin). Drosophila AMPs are synthesized by the fat body in response to infection, and secreted into the blood. Most of them can also be induced in surface epithelia in a tissue-specific manner. Finally, some of them are constitutively expressed in defined tissues, such as the salivary glands or the reproductive tract. We review here the structures and activities of these AMPs, as well as the signalling cascades, which lead to their induction upon detection of infectious non-self.}, keywords = {Animals, Antimicrobial Cationic Peptides, Defensins, Gene Expression Regulation, Genes, Glycopeptides, imler, Immunity, Innate, Insect, Insect Proteins, M3i, Molecular Structure, Signal Transduction}, pubstate = {published}, tppubtype = {article} } The production of antimicrobial peptides (AMPs) is an important aspect of host-defence in multicellular organisms. Biochemical analysis of the hemolymph of the fruit-fly Drosophila melanogaster and other Diptera has led to the discovery of eight classes of AMPs. These peptides can be grouped into three families based on their main biological targets, gram-positive bacteria (defensin), gram-negative bacteria (cecropins, drosocin, attacins, diptericin, MPAC), or fungi (drosomycin, metchnikowin). Drosophila AMPs are synthesized by the fat body in response to infection, and secreted into the blood. Most of them can also be induced in surface epithelia in a tissue-specific manner. Finally, some of them are constitutively expressed in defined tissues, such as the salivary glands or the reproductive tract. We review here the structures and activities of these AMPs, as well as the signalling cascades, which lead to their induction upon detection of infectious non-self. |
2004 |
Levy, Francine; Rabel, David; Charlet, Maurice; Bulet, Philippe; Hoffmann, Jules A; Ehret-Sabatier, Laurence Peptidomic and proteomic analyses of the systemic immune response of Drosophila Article de journal Biochimie, 86 (9-10), p. 607–616, 2004, ISSN: 0300-9084. Résumé | Liens | BibTeX | Étiquettes: Animals, hoffmann, Immunity, M3i, proteomics @article{levy_peptidomic_2004, title = {Peptidomic and proteomic analyses of the systemic immune response of Drosophila}, author = {Francine Levy and David Rabel and Maurice Charlet and Philippe Bulet and Jules A Hoffmann and Laurence Ehret-Sabatier}, doi = {10.1016/j.biochi.2004.07.007}, issn = {0300-9084}, year = {2004}, date = {2004-10-01}, journal = {Biochimie}, volume = {86}, number = {9-10}, pages = {607--616}, abstract = {Insects have developed an efficient host defense against microorganisms, which involves humoral and cellular mechanisms. Numerous data highlight similarities between defense responses of insects and innate immunity of mammals. The fruit fly, Drosophila melanogaster, is a favorable model system for the analysis of the first line defense against microorganisms. Taking advantages of improvements in mass spectrometry (MS), two-dimensional (2D) gel electrophoresis and bioinformatics, differential analyses of blood content (hemolymph) from immune-challenged versus control Drosophila were performed. Two strategies were developed: (i) peptidomic analyses through matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) MS and high performance liquid chromatography for molecules below 15 kDa, and (ii) proteomic studies based on 2D gel electrophoresis, MALDI-TOF fingerprinting and database searches, for compounds of greater molecular masses. The peptidomic strategy led to the detection of a large number of peptides induced in the hemolymph of challenged flies as compared to controls. Of these, 28 were characterized, amongst which were antimicrobial peptides. The 2D gel electrophoresis strategy led to the detection of 70 spots differentially regulated by at least fivefold after microbial infection. This approach yielded the identity of a series of proteins that were related to the Drosophila immune response, such as proteases, protease inhibitors, prophenoloxydase-activating enzymes, serpins and a Gram-negative binding protein-like protein. This strategy also brought to light new candidates with a potential function in the immune response (odorant-binding protein, peptidylglycine alpha-hydroxylating monooxygenase and transferrin). Interestingly, several molecules resulting from the cleavage of proteins were detected after a fungal infection. Together, peptidomic and proteomic analyses represent new tools to characterize molecules involved in the innate immune reactions of Drosophila.}, keywords = {Animals, hoffmann, Immunity, M3i, proteomics}, pubstate = {published}, tppubtype = {article} } Insects have developed an efficient host defense against microorganisms, which involves humoral and cellular mechanisms. Numerous data highlight similarities between defense responses of insects and innate immunity of mammals. The fruit fly, Drosophila melanogaster, is a favorable model system for the analysis of the first line defense against microorganisms. Taking advantages of improvements in mass spectrometry (MS), two-dimensional (2D) gel electrophoresis and bioinformatics, differential analyses of blood content (hemolymph) from immune-challenged versus control Drosophila were performed. Two strategies were developed: (i) peptidomic analyses through matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) MS and high performance liquid chromatography for molecules below 15 kDa, and (ii) proteomic studies based on 2D gel electrophoresis, MALDI-TOF fingerprinting and database searches, for compounds of greater molecular masses. The peptidomic strategy led to the detection of a large number of peptides induced in the hemolymph of challenged flies as compared to controls. Of these, 28 were characterized, amongst which were antimicrobial peptides. The 2D gel electrophoresis strategy led to the detection of 70 spots differentially regulated by at least fivefold after microbial infection. This approach yielded the identity of a series of proteins that were related to the Drosophila immune response, such as proteases, protease inhibitors, prophenoloxydase-activating enzymes, serpins and a Gram-negative binding protein-like protein. This strategy also brought to light new candidates with a potential function in the immune response (odorant-binding protein, peptidylglycine alpha-hydroxylating monooxygenase and transferrin). Interestingly, several molecules resulting from the cleavage of proteins were detected after a fungal infection. Together, peptidomic and proteomic analyses represent new tools to characterize molecules involved in the innate immune reactions of Drosophila. |
Irving, Phil; Troxler, Laurent; Hetru, Charles Is innate enough? The innate immune response in Drosophila Article de journal C. R. Biol., 327 (6), p. 557–570, 2004, ISSN: 1631-0691. Résumé | BibTeX | Étiquettes: Animals, bioinformatic, Immunity, Innate, M3i, Signal Transduction @article{irving_is_2004, title = {Is innate enough? The innate immune response in Drosophila}, author = {Phil Irving and Laurent Troxler and Charles Hetru}, issn = {1631-0691}, year = {2004}, date = {2004-06-01}, journal = {C. R. Biol.}, volume = {327}, number = {6}, pages = {557--570}, abstract = {In recent years, the innate immune system has emerged from the shadow of adaptive immune responses as a major area of research in its own right. One of the most significant model systems that has been used to investigate this phenomenon has been the fruit fly, Drosophila melanogaster. Exploration of the differential immune response presented by Drosophila led to the discovery of important signalling events and transduction pathways, which were thereafter shown to be specific for the type of infecting pathogen. These factors and pathways were subsequently found to have homologues in many other organisms, including those with adaptive immune responses. In light of the present status of studies in innate immunity, this review describes the current state of understanding of the Drosophila immune response.}, keywords = {Animals, bioinformatic, Immunity, Innate, M3i, Signal Transduction}, pubstate = {published}, tppubtype = {article} } In recent years, the innate immune system has emerged from the shadow of adaptive immune responses as a major area of research in its own right. One of the most significant model systems that has been used to investigate this phenomenon has been the fruit fly, Drosophila melanogaster. Exploration of the differential immune response presented by Drosophila led to the discovery of important signalling events and transduction pathways, which were thereafter shown to be specific for the type of infecting pathogen. These factors and pathways were subsequently found to have homologues in many other organisms, including those with adaptive immune responses. In light of the present status of studies in innate immunity, this review describes the current state of understanding of the Drosophila immune response. |
Leclerc, Vincent; Reichhart, Jean-Marc The immune response of Drosophila melanogaster Article de journal Immunol. Rev., 198 , p. 59–71, 2004, ISSN: 0105-2896. Résumé | BibTeX | Étiquettes: Animals, Cell Surface, Immunity, Immunological, Innate, M3i, Models, Receptors, reichhart, Signal Transduction, Toll-Like Receptors @article{leclerc_immune_2004, title = {The immune response of Drosophila melanogaster}, author = {Vincent Leclerc and Jean-Marc Reichhart}, issn = {0105-2896}, year = {2004}, date = {2004-04-01}, journal = {Immunol. Rev.}, volume = {198}, pages = {59--71}, abstract = {The response of the fruit fly Drosophila melanogaster to various microorganism infections relies on a multilayered defense. The epithelia constitute a first and efficient barrier. Innate immunity is activated when microorganisms succeed in entering the body cavity of the fly. Invading microorganisms are killed by the combined action of cellular and humoral processes. They are phagocytosed by specialized blood cells, surrounded by toxic melanin, or lysed by antibacterial peptides secreted into the hemolymph by fat body cells. During the last few years, research has focused on the mechanisms of microbial recognition by various pattern recognition receptors and of the subsequent induction of antimicrobial peptide expression. The cellular arm of the Drosophila innate immune system, which was somehow neglected, now constitutes the new frontier.}, keywords = {Animals, Cell Surface, Immunity, Immunological, Innate, M3i, Models, Receptors, reichhart, Signal Transduction, Toll-Like Receptors}, pubstate = {published}, tppubtype = {article} } The response of the fruit fly Drosophila melanogaster to various microorganism infections relies on a multilayered defense. The epithelia constitute a first and efficient barrier. Innate immunity is activated when microorganisms succeed in entering the body cavity of the fly. Invading microorganisms are killed by the combined action of cellular and humoral processes. They are phagocytosed by specialized blood cells, surrounded by toxic melanin, or lysed by antibacterial peptides secreted into the hemolymph by fat body cells. During the last few years, research has focused on the mechanisms of microbial recognition by various pattern recognition receptors and of the subsequent induction of antimicrobial peptide expression. The cellular arm of the Drosophila innate immune system, which was somehow neglected, now constitutes the new frontier. |
Blandin, Stéphanie A; Levashina, Elena A Mosquito immune responses against malaria parasites Article de journal Curr. Opin. Immunol., 16 (1), p. 16–20, 2004, ISSN: 0952-7915. Résumé | BibTeX | Étiquettes: Animals, Anopheles, blandin, Gene Library, Genes, Hemocytes, Host-Parasite Interactions, Immunity, Innate, Insect, Insect Vectors, M3i, Malaria, Plasmodium @article{blandin_mosquito_2004, title = {Mosquito immune responses against malaria parasites}, author = {Stéphanie A Blandin and Elena A Levashina}, issn = {0952-7915}, year = {2004}, date = {2004-01-01}, journal = {Curr. Opin. Immunol.}, volume = {16}, number = {1}, pages = {16--20}, abstract = {Anopheline mosquitoes are the major vectors of human malaria. Mosquito-parasite interactions are a critical aspect of disease transmission and a potential target for malaria control. Mosquitoes vary in their innate ability to support development of the malaria parasite, but the molecular mechanisms that determine vector competence are poorly understood. This area of research has been revolutionized by recent advances in the mosquito genome characterization and by the development of new tools for functional gene analysis.}, keywords = {Animals, Anopheles, blandin, Gene Library, Genes, Hemocytes, Host-Parasite Interactions, Immunity, Innate, Insect, Insect Vectors, M3i, Malaria, Plasmodium}, pubstate = {published}, tppubtype = {article} } Anopheline mosquitoes are the major vectors of human malaria. Mosquito-parasite interactions are a critical aspect of disease transmission and a potential target for malaria control. Mosquitoes vary in their innate ability to support development of the malaria parasite, but the molecular mechanisms that determine vector competence are poorly understood. This area of research has been revolutionized by recent advances in the mosquito genome characterization and by the development of new tools for functional gene analysis. |
2003 |
Royet, Julien; Reichhart, Jean-Marc Detection of peptidoglycans by NOD proteins Article de journal Trends Cell Biol., 13 (12), p. 610–614, 2003, ISSN: 0962-8924. Résumé | BibTeX | Étiquettes: Adaptor Proteins, Apoptosis, Carrier Proteins, Gram-Positive Bacteria, Humans, Immunity, Immunologic, Innate, M3i, Nod1 Signaling Adaptor Protein, Oligopeptides, peptidoglycan, Receptors, reichhart, Signal Transducing, Signal Transduction @article{royet_detection_2003, title = {Detection of peptidoglycans by NOD proteins}, author = {Julien Royet and Jean-Marc Reichhart}, issn = {0962-8924}, year = {2003}, date = {2003-12-01}, journal = {Trends Cell Biol.}, volume = {13}, number = {12}, pages = {610--614}, abstract = {Mechanisms of innate immune defense are based on the recognition of invariant microbial molecular patterns by specific receptors, followed by the activation of signaling pathways and the expression of effector molecules that will defeat the invading microorganism. Two recent reports add to the growing list of these pattern-recognition receptors by showing that the intracellular nucleotide-binding oligomerization domain 1 (NOD1) protein recognizes a diaminopimelate-containing muropeptide, a cell-wall component of Gram-negative bacteria.}, keywords = {Adaptor Proteins, Apoptosis, Carrier Proteins, Gram-Positive Bacteria, Humans, Immunity, Immunologic, Innate, M3i, Nod1 Signaling Adaptor Protein, Oligopeptides, peptidoglycan, Receptors, reichhart, Signal Transducing, Signal Transduction}, pubstate = {published}, tppubtype = {article} } Mechanisms of innate immune defense are based on the recognition of invariant microbial molecular patterns by specific receptors, followed by the activation of signaling pathways and the expression of effector molecules that will defeat the invading microorganism. Two recent reports add to the growing list of these pattern-recognition receptors by showing that the intracellular nucleotide-binding oligomerization domain 1 (NOD1) protein recognizes a diaminopimelate-containing muropeptide, a cell-wall component of Gram-negative bacteria. |
Hoffmann, Jules A The immune response of Drosophila Article de journal Nature, 426 (6962), p. 33–38, 2003, ISSN: 1476-4687. Résumé | Liens | BibTeX | Étiquettes: Animals, Cell Surface, hoffmann, Immunity, Innate, M3i, Membrane Glycoproteins, Receptors, Signal Transduction, Toll-Like Receptor 5, Toll-Like Receptors @article{hoffmann_immune_2003, title = {The immune response of Drosophila}, author = {Jules A Hoffmann}, doi = {10.1038/nature02021}, issn = {1476-4687}, year = {2003}, date = {2003-11-01}, journal = {Nature}, volume = {426}, number = {6962}, pages = {33--38}, abstract = {Drosophila mounts a potent host defence when challenged by various microorganisms. Analysis of this defence by molecular genetics has now provided a global picture of the mechanisms by which this insect senses infection, discriminates between various classes of microorganisms and induces the production of effector molecules, among which antimicrobial peptides are prominent. An unexpected result of these studies was the discovery that most of the genes involved in the Drosophila host defence are homologous or very similar to genes implicated in mammalian innate immune defences. Recent progress in research on Drosophila immune defence provides evidence for similarities and differences between Drosophila immune responses and mammalian innate immunity.}, keywords = {Animals, Cell Surface, hoffmann, Immunity, Innate, M3i, Membrane Glycoproteins, Receptors, Signal Transduction, Toll-Like Receptor 5, Toll-Like Receptors}, pubstate = {published}, tppubtype = {article} } Drosophila mounts a potent host defence when challenged by various microorganisms. Analysis of this defence by molecular genetics has now provided a global picture of the mechanisms by which this insect senses infection, discriminates between various classes of microorganisms and induces the production of effector molecules, among which antimicrobial peptides are prominent. An unexpected result of these studies was the discovery that most of the genes involved in the Drosophila host defence are homologous or very similar to genes implicated in mammalian innate immune defences. Recent progress in research on Drosophila immune defence provides evidence for similarities and differences between Drosophila immune responses and mammalian innate immunity. |
Hetru, Charles; Troxler, Laurent; Hoffmann, Jules A Drosophila melanogaster antimicrobial defense Article de journal J. Infect. Dis., 187 Suppl 2 , p. S327–334, 2003, ISSN: 0022-1899. Résumé | Liens | BibTeX | Étiquettes: Animal, Animals, Bacterial Infections, bioinformatic, hoffmann, Immunity, Innate, M3i, Mycoses, Parasitic Diseases, Peptides, Signal Transduction @article{hetru_drosophila_2003, title = {Drosophila melanogaster antimicrobial defense}, author = {Charles Hetru and Laurent Troxler and Jules A Hoffmann}, doi = {10.1086/374758}, issn = {0022-1899}, year = {2003}, date = {2003-06-01}, journal = {J. Infect. Dis.}, volume = {187 Suppl 2}, pages = {S327--334}, abstract = {The Drosophila melanogaster host defense is complex but remarkably efficient. It is a multifaceted response to a variety of fungal, bacterial, and parasitic invaders. Current knowledge is discussed on recognition of infectious microorganisms and on the activation of intracellular signaling cascades that concur with the expression of numerous immune-responsive genes, among which, to date, the most prominent appear to encode potent antimicrobial peptides.}, keywords = {Animal, Animals, Bacterial Infections, bioinformatic, hoffmann, Immunity, Innate, M3i, Mycoses, Parasitic Diseases, Peptides, Signal Transduction}, pubstate = {published}, tppubtype = {article} } The Drosophila melanogaster host defense is complex but remarkably efficient. It is a multifaceted response to a variety of fungal, bacterial, and parasitic invaders. Current knowledge is discussed on recognition of infectious microorganisms and on the activation of intracellular signaling cascades that concur with the expression of numerous immune-responsive genes, among which, to date, the most prominent appear to encode potent antimicrobial peptides. |
Kambris, Zakaria; Bilak, Hana; D'Alessandro, Rosalba; Belvin, Marcia; Imler, Jean-Luc; Capovilla, Maria DmMyD88 controls dorsoventral patterning of the Drosophila embryo Article de journal EMBO reports, 4 (1), p. 64–69, 2003, ISSN: 1469-221X. Résumé | Liens | BibTeX | Étiquettes: Adaptor Proteins, Alleles, Animals, Antigens, Base Sequence, Cell Surface, Complementary, Developmental, Differentiation, DNA, DNA Transposable Elements, Egg Proteins, Embryo, Exons, Female, Gene Expression Regulation, Genetically Modified, Genotype, imler, Immunity, Immunologic, Innate, Insertional, M3i, Male, messenger, Morphogenesis, Mutagenesis, Myeloid Differentiation Factor 88, Nonmammalian, Oocytes, Protein Biosynthesis, Protein Structure, Receptors, Reverse Transcriptase Polymerase Chain Reaction, RNA, Signal Transducing, Tertiary, Toll-Like Receptors, Zygote @article{kambris_dmmyd88_2003, title = {DmMyD88 controls dorsoventral patterning of the Drosophila embryo}, author = {Zakaria Kambris and Hana Bilak and Rosalba D'Alessandro and Marcia Belvin and Jean-Luc Imler and Maria Capovilla}, doi = {10.1038/sj.embor.embor714}, issn = {1469-221X}, year = {2003}, date = {2003-01-01}, journal = {EMBO reports}, volume = {4}, number = {1}, pages = {64--69}, abstract = {MyD88 is an adapter protein in the signal transduction pathway mediated by interleukin-1 (IL-1) and Toll-like receptors. A Drosophila homologue of MyD88 (DmMyD88) was recently shown to be required for the Toll-mediated immune response. In Drosophila, the Toll pathway was originally characterized for its role in the dorsoventral patterning of the embryo. We found that, like Toll, DmMyD88 messenger RNA is maternally supplied to the embryo. Here we report the identification of a new mutant allele of DmMyD88, which generates a protein lacking the carboxy-terminal extension, normally located downstream of the Toll/IL-1 receptor domain. Homozygous mutant female flies lay dorsalized embryos that are rescued by expression of a transgenic DmMyD88 complementary DNA. The DmMyD88 mutation blocks the ventralizing activity of a gain-of-function Toll mutation. These results show that DmMyD88 encodes an essential component of the Toll pathway in dorsoventral pattern formation.}, keywords = {Adaptor Proteins, Alleles, Animals, Antigens, Base Sequence, Cell Surface, Complementary, Developmental, Differentiation, DNA, DNA Transposable Elements, Egg Proteins, Embryo, Exons, Female, Gene Expression Regulation, Genetically Modified, Genotype, imler, Immunity, Immunologic, Innate, Insertional, M3i, Male, messenger, Morphogenesis, Mutagenesis, Myeloid Differentiation Factor 88, Nonmammalian, Oocytes, Protein Biosynthesis, Protein Structure, Receptors, Reverse Transcriptase Polymerase Chain Reaction, RNA, Signal Transducing, Tertiary, Toll-Like Receptors, Zygote}, pubstate = {published}, tppubtype = {article} } MyD88 is an adapter protein in the signal transduction pathway mediated by interleukin-1 (IL-1) and Toll-like receptors. A Drosophila homologue of MyD88 (DmMyD88) was recently shown to be required for the Toll-mediated immune response. In Drosophila, the Toll pathway was originally characterized for its role in the dorsoventral patterning of the embryo. We found that, like Toll, DmMyD88 messenger RNA is maternally supplied to the embryo. Here we report the identification of a new mutant allele of DmMyD88, which generates a protein lacking the carboxy-terminal extension, normally located downstream of the Toll/IL-1 receptor domain. Homozygous mutant female flies lay dorsalized embryos that are rescued by expression of a transgenic DmMyD88 complementary DNA. The DmMyD88 mutation blocks the ventralizing activity of a gain-of-function Toll mutation. These results show that DmMyD88 encodes an essential component of the Toll pathway in dorsoventral pattern formation. |
2002 |
Naitza, Silvia; Rossé, Carine; Kappler, Christine; Georgel, Philippe; Belvin, Marcia; Gubb, David; Camonis, Jacques; Hoffmann, Jules A; Reichhart, Jean-Marc The Drosophila immune defense against gram-negative infection requires the death protein dFADD Article de journal Immunity, 17 (5), p. 575–581, 2002, ISSN: 1074-7613. Résumé | BibTeX | Étiquettes: Adaptor Proteins, Animals, Carrier Proteins, Fas-Associated Death Domain Protein, Gene Expression Regulation, Gram-Negative Bacterial Infections, hoffmann, Immunity, M3i, reichhart, Signal Transducing, Signal Transduction @article{naitza_drosophila_2002, title = {The Drosophila immune defense against gram-negative infection requires the death protein dFADD}, author = {Silvia Naitza and Carine Rossé and Christine Kappler and Philippe Georgel and Marcia Belvin and David Gubb and Jacques Camonis and Jules A Hoffmann and Jean-Marc Reichhart}, issn = {1074-7613}, year = {2002}, date = {2002-11-01}, journal = {Immunity}, volume = {17}, number = {5}, pages = {575--581}, abstract = {Drosophila responds to Gram-negative infections by mounting an immune response that depends on components of the IMD pathway. We recently showed that imd encodes a protein with a death domain with high similarity to that of mammalian RIP. Using a two-hybrid screen in yeast, we have isolated the death protein dFADD as a molecule that associates with IMD. Our data show that loss of dFADD function renders flies highly susceptible to Gram-negative infections without affecting resistance to Gram-positive bacteria. By genetic analysis we show that dFADD acts downstream of IMD in the pathway that controls inducibility of the antibacterial peptide genes.}, keywords = {Adaptor Proteins, Animals, Carrier Proteins, Fas-Associated Death Domain Protein, Gene Expression Regulation, Gram-Negative Bacterial Infections, hoffmann, Immunity, M3i, reichhart, Signal Transducing, Signal Transduction}, pubstate = {published}, tppubtype = {article} } Drosophila responds to Gram-negative infections by mounting an immune response that depends on components of the IMD pathway. We recently showed that imd encodes a protein with a death domain with high similarity to that of mammalian RIP. Using a two-hybrid screen in yeast, we have isolated the death protein dFADD as a molecule that associates with IMD. Our data show that loss of dFADD function renders flies highly susceptible to Gram-negative infections without affecting resistance to Gram-positive bacteria. By genetic analysis we show that dFADD acts downstream of IMD in the pathway that controls inducibility of the antibacterial peptide genes. |
Christophides, George K; Zdobnov, Evgeny; Barillas-Mury, Carolina; Birney, Ewan; Blandin, Stephanie A; Blass, Claudia; Brey, Paul T; Collins, Frank H; Danielli, Alberto; Dimopoulos, George; Hetru, Charles; Hoa, Ngo T; Hoffmann, Jules A; Kanzok, Stefan M; Letunic, Ivica; Levashina, Elena A; Loukeris, Thanasis G; Lycett, Gareth; Meister, Stephan; Michel, Kristin; Moita, Luis F; Müller, Hans-Michael; Osta, Mike A; Paskewitz, Susan M; Reichhart, Jean-Marc; Rzhetsky, Andrey; Troxler, Laurent; Vernick, Kenneth D; Vlachou, Dina; Volz, Jennifer; von Mering, Christian; Xu, Jiannong; Zheng, Liangbiao; Bork, Peer; Kafatos, Fotis C Immunity-related genes and gene families in Anopheles gambiae Article de journal Science, 298 (5591), p. 159–165, 2002, ISSN: 1095-9203. Résumé | Liens | BibTeX | Étiquettes: Alternative Splicing, Animals, Anopheles, Apoptosis, bacteria, bioinformatic, blandin, Catechol Oxidase, Computational Biology, Enzyme Precursors, Gene Expression Regulation, Genes, Genetic, Genome, hoffmann, Immunity, Innate, Insect, Insect Proteins, M3i, Multigene Family, Peptides, Phylogeny, Plasmodium, Protein Structure, reichhart, Selection, Serine Endopeptidases, Serpins, Signal Transduction, Tertiary @article{christophides_immunity-related_2002, title = {Immunity-related genes and gene families in Anopheles gambiae}, author = {George K Christophides and Evgeny Zdobnov and Carolina Barillas-Mury and Ewan Birney and Stephanie A Blandin and Claudia Blass and Paul T Brey and Frank H Collins and Alberto Danielli and George Dimopoulos and Charles Hetru and Ngo T Hoa and Jules A Hoffmann and Stefan M Kanzok and Ivica Letunic and Elena A Levashina and Thanasis G Loukeris and Gareth Lycett and Stephan Meister and Kristin Michel and Luis F Moita and Hans-Michael Müller and Mike A Osta and Susan M Paskewitz and Jean-Marc Reichhart and Andrey Rzhetsky and Laurent Troxler and Kenneth D Vernick and Dina Vlachou and Jennifer Volz and Christian von Mering and Jiannong Xu and Liangbiao Zheng and Peer Bork and Fotis C Kafatos}, url = {http://www.ncbi.nlm.nih.gov/pubmed/12364793}, doi = {10.1126/science.1077136}, issn = {1095-9203}, year = {2002}, date = {2002-10-01}, journal = {Science}, volume = {298}, number = {5591}, pages = {159--165}, abstract = {We have identified 242 Anopheles gambiae genes from 18 gene families implicated in innate immunity and have detected marked diversification relative to Drosophila melanogaster. Immune-related gene families involved in recognition, signal modulation, and effector systems show a marked deficit of orthologs and excessive gene expansions, possibly reflecting selection pressures from different pathogens encountered in these insects' very different life-styles. In contrast, the multifunctional Toll signal transduction pathway is substantially conserved, presumably because of counterselection for developmental stability. Representative expression profiles confirm that sequence diversification is accompanied by specific responses to different immune challenges. Alternative RNA splicing may also contribute to expansion of the immune repertoire.}, keywords = {Alternative Splicing, Animals, Anopheles, Apoptosis, bacteria, bioinformatic, blandin, Catechol Oxidase, Computational Biology, Enzyme Precursors, Gene Expression Regulation, Genes, Genetic, Genome, hoffmann, Immunity, Innate, Insect, Insect Proteins, M3i, Multigene Family, Peptides, Phylogeny, Plasmodium, Protein Structure, reichhart, Selection, Serine Endopeptidases, Serpins, Signal Transduction, Tertiary}, pubstate = {published}, tppubtype = {article} } We have identified 242 Anopheles gambiae genes from 18 gene families implicated in innate immunity and have detected marked diversification relative to Drosophila melanogaster. Immune-related gene families involved in recognition, signal modulation, and effector systems show a marked deficit of orthologs and excessive gene expansions, possibly reflecting selection pressures from different pathogens encountered in these insects' very different life-styles. In contrast, the multifunctional Toll signal transduction pathway is substantially conserved, presumably because of counterselection for developmental stability. Representative expression profiles confirm that sequence diversification is accompanied by specific responses to different immune challenges. Alternative RNA splicing may also contribute to expansion of the immune repertoire. |
Hoffmann, Jules A; Reichhart, Jean-Marc Drosophila innate immunity: an evolutionary perspective Article de journal Nat. Immunol., 3 (2), p. 121–126, 2002, ISSN: 1529-2908. Résumé | Liens | BibTeX | Étiquettes: Animals, Biological Evolution, Cell Surface, hoffmann, Immunity, Immunological, Innate, M3i, Membrane Glycoproteins, Models, Receptors, reichhart, Signal Transduction, Toll-Like Receptors @article{hoffmann_drosophila_2002, title = {Drosophila innate immunity: an evolutionary perspective}, author = {Jules A Hoffmann and Jean-Marc Reichhart}, doi = {10.1038/ni0202-121}, issn = {1529-2908}, year = {2002}, date = {2002-02-01}, journal = {Nat. Immunol.}, volume = {3}, number = {2}, pages = {121--126}, abstract = {In response to microbial infections, Drosophila mounts a multifaceted immune response involving humoral reactions that culminate in the destruction of invading organisms by lytic peptides. These defense mechanisms are activated via two distinct signaling pathways. One of these, the Toll pathway, controls resistance to fungal and Gram-positive bacterial infections, whereas the Imd pathway is responsible for defense against Gram-negative bacterial infections. Current evidence indicates that recognition of infectious nonself agents results from interactions between microbial wall components and extracellular pattern recognition proteins. We discuss here evolutionary perspectives on our present understanding of the antimicrobial defenses of Drosophila.}, keywords = {Animals, Biological Evolution, Cell Surface, hoffmann, Immunity, Immunological, Innate, M3i, Membrane Glycoproteins, Models, Receptors, reichhart, Signal Transduction, Toll-Like Receptors}, pubstate = {published}, tppubtype = {article} } In response to microbial infections, Drosophila mounts a multifaceted immune response involving humoral reactions that culminate in the destruction of invading organisms by lytic peptides. These defense mechanisms are activated via two distinct signaling pathways. One of these, the Toll pathway, controls resistance to fungal and Gram-positive bacterial infections, whereas the Imd pathway is responsible for defense against Gram-negative bacterial infections. Current evidence indicates that recognition of infectious nonself agents results from interactions between microbial wall components and extracellular pattern recognition proteins. We discuss here evolutionary perspectives on our present understanding of the antimicrobial defenses of Drosophila. |
2001 |
Imler, Jean-Luc; Hoffmann, Jules A Toll receptors in innate immunity Article de journal Trends in Cell Biology, 11 (7), p. 304–311, 2001, ISSN: 0962-8924. Résumé | BibTeX | Étiquettes: Animals, Cell Surface, hoffmann, Humans, imler, Immunity, Immunologic, Innate, M3i, Membrane Glycoproteins, Membrane Proteins, Receptors, Toll-Like Receptors @article{imler_toll_2001, title = {Toll receptors in innate immunity}, author = {Jean-Luc Imler and Jules A Hoffmann}, issn = {0962-8924}, year = {2001}, date = {2001-01-01}, journal = {Trends in Cell Biology}, volume = {11}, number = {7}, pages = {304--311}, abstract = {Innate immunity is the first-line host defense of multicellular organisms that rapidly operates to limit infection upon exposure to infectious agents. In addition, the cells and molecules operating during this early stage of the immune response in vertebrates have a decisive impact on the shaping of the subsequent adaptive response. Genetic studies initially performed in the fruitfly Drosophila and later in mice have revealed the importance of proteins of the Toll family in the innate immune response. We present here our current understanding of the role of this evolutionary ancient family of proteins that are thought to function as cytokine receptors (Toll in Drosophila) or pattern-recognition receptors (TLRs in mammals) and activate similar, albeit non-identical, signal-transduction pathways in flies and mammals.}, keywords = {Animals, Cell Surface, hoffmann, Humans, imler, Immunity, Immunologic, Innate, M3i, Membrane Glycoproteins, Membrane Proteins, Receptors, Toll-Like Receptors}, pubstate = {published}, tppubtype = {article} } Innate immunity is the first-line host defense of multicellular organisms that rapidly operates to limit infection upon exposure to infectious agents. In addition, the cells and molecules operating during this early stage of the immune response in vertebrates have a decisive impact on the shaping of the subsequent adaptive response. Genetic studies initially performed in the fruitfly Drosophila and later in mice have revealed the importance of proteins of the Toll family in the innate immune response. We present here our current understanding of the role of this evolutionary ancient family of proteins that are thought to function as cytokine receptors (Toll in Drosophila) or pattern-recognition receptors (TLRs in mammals) and activate similar, albeit non-identical, signal-transduction pathways in flies and mammals. |
2000 |
Rutschmann, Sophie; Jung, Alain C; Zhou, R; Silverman, N; Hoffmann, Jules A; Ferrandon, Dominique Role of Drosophila IKK gamma in a toll-independent antibacterial immune response Article de journal Nat. Immunol., 1 (4), p. 342–347, 2000, ISSN: 1529-2908. Résumé | Liens | BibTeX | Étiquettes: Animals, Antigens, Bacterial, Cell Surface, ferrandon, Gene Expression Regulation, hoffmann, I-kappa B Kinase, Immunity, Innate, Insect Proteins, M3i, Membrane Glycoproteins, Protein-Serine-Threonine Kinases, Receptors, Signal Transduction, Toll-Like Receptors, Transcription Factors @article{rutschmann_role_2000, title = {Role of Drosophila IKK gamma in a toll-independent antibacterial immune response}, author = {Sophie Rutschmann and Alain C Jung and R Zhou and N Silverman and Jules A Hoffmann and Dominique Ferrandon}, doi = {10.1038/79801}, issn = {1529-2908}, year = {2000}, date = {2000-10-01}, journal = {Nat. Immunol.}, volume = {1}, number = {4}, pages = {342--347}, abstract = {We have generated, by ethylmethane sulfonate mutagenesis, loss-of-function mutants in the Drosophila homolog of the mammalian I-kappa B kinase (IKK) complex component IKK gamma (also called NEMO). Our data show that Drosophila IKK gamma is required for the Relish-dependent immune induction of the genes encoding antibacterial peptides and for resistance to infections by Escherichia coli. However, it is not required for the Toll-DIF-dependent antifungal host defense. The results indicate distinct control mechanisms of the Rel-like transactivators DIF and Relish in the Drosophila innate immune response and show that Drosophila Toll does not signal through a IKK gamma-dependent signaling complex. Thus, in contrast to the vertebrate inflammatory response, IKK gamma is required for the activation of only one immune signaling pathway in Drosophila.}, keywords = {Animals, Antigens, Bacterial, Cell Surface, ferrandon, Gene Expression Regulation, hoffmann, I-kappa B Kinase, Immunity, Innate, Insect Proteins, M3i, Membrane Glycoproteins, Protein-Serine-Threonine Kinases, Receptors, Signal Transduction, Toll-Like Receptors, Transcription Factors}, pubstate = {published}, tppubtype = {article} } We have generated, by ethylmethane sulfonate mutagenesis, loss-of-function mutants in the Drosophila homolog of the mammalian I-kappa B kinase (IKK) complex component IKK gamma (also called NEMO). Our data show that Drosophila IKK gamma is required for the Relish-dependent immune induction of the genes encoding antibacterial peptides and for resistance to infections by Escherichia coli. However, it is not required for the Toll-DIF-dependent antifungal host defense. The results indicate distinct control mechanisms of the Rel-like transactivators DIF and Relish in the Drosophila innate immune response and show that Drosophila Toll does not signal through a IKK gamma-dependent signaling complex. Thus, in contrast to the vertebrate inflammatory response, IKK gamma is required for the activation of only one immune signaling pathway in Drosophila. |
Rutschmann, Sophie; Jung, Alain C; Hetru, Charles; Reichhart, Jean-Marc; Hoffmann, Jules A; Ferrandon, Dominique The Rel protein DIF mediates the antifungal but not the antibacterial host defense in Drosophila Article de journal Immunity, 12 (5), p. 569–580, 2000, ISSN: 1074-7613. Résumé | BibTeX | Étiquettes: Animals, Antigens, Bacterial, DNA-Binding Proteins, ferrandon, Fungal, hoffmann, Immunity, Innate, M3i, reichhart, Transcription Factors @article{rutschmann_rel_2000, title = {The Rel protein DIF mediates the antifungal but not the antibacterial host defense in Drosophila}, author = {Sophie Rutschmann and Alain C Jung and Charles Hetru and Jean-Marc Reichhart and Jules A Hoffmann and Dominique Ferrandon}, issn = {1074-7613}, year = {2000}, date = {2000-05-01}, journal = {Immunity}, volume = {12}, number = {5}, pages = {569--580}, abstract = {We have isolated two Drosophila lines that carry point mutations in the gene coding for the NF-KB-like factor DIF. Like mutants of the Toll pathway, Dif mutant flies are susceptible to fungal but not to bacterial infections. Genetic epistasis experiments demonstrate that Dif mediates the Toll-dependent control of the inducibility of the antifungal peptide gene Drosomycin. Strikingly, DIF alone is required for the antifungal response in adults, but is redundant in larvae with Dorsal, another Rel family member. In Drosophila, Dif appears to be dedicated to the antifungal defense elicited by fungi and gram-positive bacteria. We discuss in this light the possibility that NF-KB1/p50 might be required more specifically in the innate immune response against gram-positive bacteria in mammals.}, keywords = {Animals, Antigens, Bacterial, DNA-Binding Proteins, ferrandon, Fungal, hoffmann, Immunity, Innate, M3i, reichhart, Transcription Factors}, pubstate = {published}, tppubtype = {article} } We have isolated two Drosophila lines that carry point mutations in the gene coding for the NF-KB-like factor DIF. Like mutants of the Toll pathway, Dif mutant flies are susceptible to fungal but not to bacterial infections. Genetic epistasis experiments demonstrate that Dif mediates the Toll-dependent control of the inducibility of the antifungal peptide gene Drosomycin. Strikingly, DIF alone is required for the antifungal response in adults, but is redundant in larvae with Dorsal, another Rel family member. In Drosophila, Dif appears to be dedicated to the antifungal defense elicited by fungi and gram-positive bacteria. We discuss in this light the possibility that NF-KB1/p50 might be required more specifically in the innate immune response against gram-positive bacteria in mammals. |
Imler, Jean-Luc; Hoffmann, Jules A Toll and Toll-like proteins: an ancient family of receptors signaling infection Article de journal Reviews in Immunogenetics, 2 (3), p. 294–304, 2000, ISSN: 1398-1714. Résumé | BibTeX | Étiquettes: Adaptor Proteins, Animals, Antigens, Autoantigens, CD14, Cell Adhesion Molecules, Cell Surface, Differentiation, DNA-Binding Proteins, Gene Expression Regulation, hoffmann, I-kappa B Proteins, imler, Immunity, Immunologic, infection, Innate, Insect Proteins, Interleukin-1 Receptor-Associated Kinases, Knockout, Larva, Lipopolysaccharides, M3i, Mammals, MAP Kinase Signaling System, Membrane Glycoproteins, Membrane Proteins, Mice, Multigene Family, Myeloid Differentiation Factor 88, NF-kappa B, peptidoglycan, Phosphorylation, Post-Translational, Protein Kinases, Protein Processing, Protein Structure, Receptors, Recombinant Fusion Proteins, Signal Transducing, Signal Transduction, Teichoic Acids, Tertiary, Toll-Like Receptor 4, Toll-Like Receptor 5, Toll-Like Receptor 6, Toll-Like Receptor 9, Toll-Like Receptors, Ubiquitins @article{imler_toll_2000, title = {Toll and Toll-like proteins: an ancient family of receptors signaling infection}, author = {Jean-Luc Imler and Jules A Hoffmann}, issn = {1398-1714}, year = {2000}, date = {2000-01-01}, journal = {Reviews in Immunogenetics}, volume = {2}, number = {3}, pages = {294--304}, abstract = {Innate immunity is the first-line host defense of multicellular organisms that rapidly operates to limit infection upon exposure to microbes. It involves intracellular signaling pathways in the fruit-fly Drosophila and in mammals that show striking similarities. Recent genetic and biochemical data have revealed, in particular, that proteins of the Toll family play a critical role in the immediate response to infection. We review here the recent developments on the structural and functional characterization of this evolutionary ancient and important family of proteins, which can function as cytokine receptors (Toll in Drosophila) or pattern recognition receptors (TLR4 in mammals) and activate similar, albeit non identical signal transduction pathways, in flies and mammals.}, keywords = {Adaptor Proteins, Animals, Antigens, Autoantigens, CD14, Cell Adhesion Molecules, Cell Surface, Differentiation, DNA-Binding Proteins, Gene Expression Regulation, hoffmann, I-kappa B Proteins, imler, Immunity, Immunologic, infection, Innate, Insect Proteins, Interleukin-1 Receptor-Associated Kinases, Knockout, Larva, Lipopolysaccharides, M3i, Mammals, MAP Kinase Signaling System, Membrane Glycoproteins, Membrane Proteins, Mice, Multigene Family, Myeloid Differentiation Factor 88, NF-kappa B, peptidoglycan, Phosphorylation, Post-Translational, Protein Kinases, Protein Processing, Protein Structure, Receptors, Recombinant Fusion Proteins, Signal Transducing, Signal Transduction, Teichoic Acids, Tertiary, Toll-Like Receptor 4, Toll-Like Receptor 5, Toll-Like Receptor 6, Toll-Like Receptor 9, Toll-Like Receptors, Ubiquitins}, pubstate = {published}, tppubtype = {article} } Innate immunity is the first-line host defense of multicellular organisms that rapidly operates to limit infection upon exposure to microbes. It involves intracellular signaling pathways in the fruit-fly Drosophila and in mammals that show striking similarities. Recent genetic and biochemical data have revealed, in particular, that proteins of the Toll family play a critical role in the immediate response to infection. We review here the recent developments on the structural and functional characterization of this evolutionary ancient and important family of proteins, which can function as cytokine receptors (Toll in Drosophila) or pattern recognition receptors (TLR4 in mammals) and activate similar, albeit non identical signal transduction pathways, in flies and mammals. |