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2015 |
Paro, Simona; Imler, Jean-Luc; Meignin, Carine Sensing viral RNAs by Dicer/RIG-I like ATPases across species Article de journal Current Opinion in Immunology, 32 , p. 106–113, 2015, ISSN: 1879-0372. Résumé | Liens | BibTeX | Étiquettes: Adenosine Triphosphatases, Animals, DEAD-box RNA Helicases, Humans, imler, M3i, meignin, Protein Binding, Protein Interaction Domains and Motifs, Ribonuclease III, RNA, Viral, Virus Diseases, viruses @article{paro_sensing_2015, title = {Sensing viral RNAs by Dicer/RIG-I like ATPases across species}, author = {Simona Paro and Jean-Luc Imler and Carine Meignin}, url = {http://linkinghub.elsevier.com/retrieve/pii/S0952791515000102}, doi = {10.1016/j.coi.2015.01.009}, issn = {1879-0372}, year = {2015}, date = {2015-02-01}, journal = {Current Opinion in Immunology}, volume = {32}, pages = {106--113}, abstract = {Induction of antiviral immunity in vertebrates and invertebrates relies on members of the RIG-I-like receptor and Dicer families, respectively. Although these proteins have different size and domain composition, members of both families share a conserved DECH-box helicase domain. This helicase, also known as a duplex RNA activated ATPase, or DRA domain, plays an important role in viral RNA sensing. Crystallographic and electron microscopy studies of the RIG-I and Dicer DRA domains indicate a common structure and that similar conformational changes are induced by dsRNA binding. Genetic and biochemical studies on the function and regulation of DRAs reveal similarities, but also some differences, between viral RNA sensing mechanisms in nematodes, flies and mammals.}, keywords = {Adenosine Triphosphatases, Animals, DEAD-box RNA Helicases, Humans, imler, M3i, meignin, Protein Binding, Protein Interaction Domains and Motifs, Ribonuclease III, RNA, Viral, Virus Diseases, viruses}, pubstate = {published}, tppubtype = {article} } Induction of antiviral immunity in vertebrates and invertebrates relies on members of the RIG-I-like receptor and Dicer families, respectively. Although these proteins have different size and domain composition, members of both families share a conserved DECH-box helicase domain. This helicase, also known as a duplex RNA activated ATPase, or DRA domain, plays an important role in viral RNA sensing. Crystallographic and electron microscopy studies of the RIG-I and Dicer DRA domains indicate a common structure and that similar conformational changes are induced by dsRNA binding. Genetic and biochemical studies on the function and regulation of DRAs reveal similarities, but also some differences, between viral RNA sensing mechanisms in nematodes, flies and mammals. |
2014 |
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. |
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 |
Fukuyama, Hidehiro; Verdier, Yann; Guan, Yongsheng; Makino-Okamura, Chieko; Shilova, Victoria; Liu, Xi; Maksoud, Elie; Matsubayashi, Jun; Haddad, Iman; Spirohn, Kerstin; Ono, Kenichiro; Hetru, Charles; Rossier, Jean; Ideker, Trey; Boutros, Michael; Vinh, Joëlle; Hoffmann, Jules A Landscape of protein-protein interactions in Drosophila immune deficiency signaling during bacterial challenge Article de journal Proc. Natl. Acad. Sci. U.S.A., 110 (26), p. 10717–10722, 2013, ISSN: 1091-6490. Résumé | Liens | BibTeX | Étiquettes: Amino Acid, Animals, Chromatin Assembly and Disassembly, Escherichia coli, functional proteomics, Genes, Genetically Modified, Histone Acetyltransferases, hoffmann, Host-Pathogen Interactions, Humans, IMD interactome, Insect, M3i, Models, Molecular, Protein Interaction Maps, Sequence Homology, Signal Transduction, small ubiquitin-like modifier @article{fukuyama_landscape_2013, title = {Landscape of protein-protein interactions in Drosophila immune deficiency signaling during bacterial challenge}, author = {Hidehiro Fukuyama and Yann Verdier and Yongsheng Guan and Chieko Makino-Okamura and Victoria Shilova and Xi Liu and Elie Maksoud and Jun Matsubayashi and Iman Haddad and Kerstin Spirohn and Kenichiro Ono and Charles Hetru and Jean Rossier and Trey Ideker and Michael Boutros and Joëlle Vinh and Jules A Hoffmann}, doi = {10.1073/pnas.1304380110}, issn = {1091-6490}, year = {2013}, date = {2013-06-01}, journal = {Proc. Natl. Acad. Sci. U.S.A.}, volume = {110}, number = {26}, pages = {10717--10722}, abstract = {The Drosophila defense against pathogens largely relies on the activation of two signaling pathways: immune deficiency (IMD) and Toll. The IMD pathway is triggered mainly by Gram-negative bacteria, whereas the Toll pathway responds predominantly to Gram-positive bacteria and fungi. The activation of these pathways leads to the rapid induction of numerous NF-κB-induced immune response genes, including antimicrobial peptide genes. The IMD pathway shows significant similarities with the TNF receptor pathway. Recent evidence indicates that the IMD pathway is also activated in response to various noninfectious stimuli (i.e., inflammatory-like reactions). To gain a better understanding of the molecular machinery underlying the pleiotropic functions of this pathway, we first performed a comprehensive proteomics analysis to identify the proteins interacting with the 11 canonical members of the pathway initially identified by genetic studies. We identified 369 interacting proteins (corresponding to 291 genes) in heat-killed Escherichia coli-stimulated Drosophila S2 cells, 92% of which have human orthologs. A comparative analysis of gene ontology from fly or human gene annotation databases points to four significant common categories: (i) the NuA4, nucleosome acetyltransferase of H4, histone acetyltransferase complex, (ii) the switching defective/sucrose nonfermenting-type chromatin remodeling complex, (iii) transcription coactivator activity, and (iv) translation factor activity. Here we demonstrate that sumoylation of the IκB kinase homolog immune response-deficient 5 plays an important role in the induction of antimicrobial peptide genes through a highly conserved sumoylation consensus site during bacterial challenge. Taken together, the proteomics data presented here provide a unique avenue for a comparative functional analysis of proteins involved in innate immune reactions in flies and mammals.}, keywords = {Amino Acid, Animals, Chromatin Assembly and Disassembly, Escherichia coli, functional proteomics, Genes, Genetically Modified, Histone Acetyltransferases, hoffmann, Host-Pathogen Interactions, Humans, IMD interactome, Insect, M3i, Models, Molecular, Protein Interaction Maps, Sequence Homology, Signal Transduction, small ubiquitin-like modifier}, pubstate = {published}, tppubtype = {article} } The Drosophila defense against pathogens largely relies on the activation of two signaling pathways: immune deficiency (IMD) and Toll. The IMD pathway is triggered mainly by Gram-negative bacteria, whereas the Toll pathway responds predominantly to Gram-positive bacteria and fungi. The activation of these pathways leads to the rapid induction of numerous NF-κB-induced immune response genes, including antimicrobial peptide genes. The IMD pathway shows significant similarities with the TNF receptor pathway. Recent evidence indicates that the IMD pathway is also activated in response to various noninfectious stimuli (i.e., inflammatory-like reactions). To gain a better understanding of the molecular machinery underlying the pleiotropic functions of this pathway, we first performed a comprehensive proteomics analysis to identify the proteins interacting with the 11 canonical members of the pathway initially identified by genetic studies. We identified 369 interacting proteins (corresponding to 291 genes) in heat-killed Escherichia coli-stimulated Drosophila S2 cells, 92% of which have human orthologs. A comparative analysis of gene ontology from fly or human gene annotation databases points to four significant common categories: (i) the NuA4, nucleosome acetyltransferase of H4, histone acetyltransferase complex, (ii) the switching defective/sucrose nonfermenting-type chromatin remodeling complex, (iii) transcription coactivator activity, and (iv) translation factor activity. Here we demonstrate that sumoylation of the IκB kinase homolog immune response-deficient 5 plays an important role in the induction of antimicrobial peptide genes through a highly conserved sumoylation consensus site during bacterial challenge. Taken together, the proteomics data presented here provide a unique avenue for a comparative functional analysis of proteins involved in innate immune reactions in flies and mammals. |
Kobayashi, Taira; Ogawa, Michinaga; Sanada, Takahito; Mimuro, Hitomi; Kim, Minsoo; Ashida, Hiroshi; Akakura, Reiko; Yoshida, Mitsutaka; Kawalec, Magdalena; Reichhart, Jean-Marc; Mizushima, Tsunehiro; Sasakawa, Chihiro The Shigella OspC3 effector inhibits caspase-4, antagonizes inflammatory cell death, and promotes epithelial infection Article de journal Cell Host Microbe, 13 (5), p. 570–583, 2013, ISSN: 1934-6069. Résumé | Liens | BibTeX | Étiquettes: Animal, Animals, Bacillary, Bacterial, Bacterial Proteins, Caspases, Cell Death, Cell Line, Disease Models, DNA, Dysentery, Enzyme Inhibitors, Epithelial Cells, Escherichia coli, Gene Knockout Techniques, Guinea Pigs, Host-Pathogen Interactions, Humans, Initiator, M3i, Protein Binding, Protein Interaction Mapping, reichhart, Salmonella typhimurium, Sequence Analysis, Shigella flexneri, Virulence Factors @article{kobayashi_shigella_2013, title = {The Shigella OspC3 effector inhibits caspase-4, antagonizes inflammatory cell death, and promotes epithelial infection}, author = {Taira Kobayashi and Michinaga Ogawa and Takahito Sanada and Hitomi Mimuro and Minsoo Kim and Hiroshi Ashida and Reiko Akakura and Mitsutaka Yoshida and Magdalena Kawalec and Jean-Marc Reichhart and Tsunehiro Mizushima and Chihiro Sasakawa}, doi = {10.1016/j.chom.2013.04.012}, issn = {1934-6069}, year = {2013}, date = {2013-05-01}, journal = {Cell Host Microbe}, volume = {13}, number = {5}, pages = {570--583}, abstract = {Caspase-mediated inflammatory cell death acts as an intrinsic defense mechanism against infection. Bacterial pathogens deploy countermeasures against inflammatory cell death, but the mechanisms by which they do this remain largely unclear. In a screen for Shigella flexneri effectors that regulate cell death during infection, we discovered that Shigella infection induced acute inflammatory, caspase-4-dependent epithelial cell death, which is counteracted by the bacterial OspC3 effector. OspC3 interacts with the caspase-4-p19 subunit and inhibits its activation by preventing caspase-4-p19 and caspase-4-p10 heterodimerization by depositing the conserved OspC3 X1-Y-X₂-D-X₃ motif at the putative catalytic pocket of caspase-4. Infection of guinea pigs with a Shigella ospC3-deficient mutant resulted in enhanced inflammatory cell death and associated symptoms, correlating with decreased bacterial burdens. Salmonella Typhimurium and enteropathogenic Escherichia coli infection also induced caspase-4-dependent epithelial death. These findings highlight the importance of caspase-4-dependent innate immune responses and demonstrate that Shigella delivers a caspase-4-specific inhibitor to delay epithelial cell death and promote infection.}, keywords = {Animal, Animals, Bacillary, Bacterial, Bacterial Proteins, Caspases, Cell Death, Cell Line, Disease Models, DNA, Dysentery, Enzyme Inhibitors, Epithelial Cells, Escherichia coli, Gene Knockout Techniques, Guinea Pigs, Host-Pathogen Interactions, Humans, Initiator, M3i, Protein Binding, Protein Interaction Mapping, reichhart, Salmonella typhimurium, Sequence Analysis, Shigella flexneri, Virulence Factors}, pubstate = {published}, tppubtype = {article} } Caspase-mediated inflammatory cell death acts as an intrinsic defense mechanism against infection. Bacterial pathogens deploy countermeasures against inflammatory cell death, but the mechanisms by which they do this remain largely unclear. In a screen for Shigella flexneri effectors that regulate cell death during infection, we discovered that Shigella infection induced acute inflammatory, caspase-4-dependent epithelial cell death, which is counteracted by the bacterial OspC3 effector. OspC3 interacts with the caspase-4-p19 subunit and inhibits its activation by preventing caspase-4-p19 and caspase-4-p10 heterodimerization by depositing the conserved OspC3 X1-Y-X₂-D-X₃ motif at the putative catalytic pocket of caspase-4. Infection of guinea pigs with a Shigella ospC3-deficient mutant resulted in enhanced inflammatory cell death and associated symptoms, correlating with decreased bacterial burdens. Salmonella Typhimurium and enteropathogenic Escherichia coli infection also induced caspase-4-dependent epithelial death. These findings highlight the importance of caspase-4-dependent innate immune responses and demonstrate that Shigella delivers a caspase-4-specific inhibitor to delay epithelial cell death and promote infection. |
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). |
2012 |
Meister, Marie; Ferrandon, Dominique Immune cell transdifferentiation: a complex crosstalk between circulating immune cells and the haematopoietic niche Article de journal EMBO Rep., 13 (1), p. 3–4, 2012, ISSN: 1469-3178. Liens | BibTeX | Étiquettes: Animals, Cell Communication, Cell Transdifferentiation, ferrandon, Hematopoietic Stem Cells, Humans, Immune System, M3i, Signal Transduction, Stem Cell Niche @article{meister_immune_2012, title = {Immune cell transdifferentiation: a complex crosstalk between circulating immune cells and the haematopoietic niche}, author = {Marie Meister and Dominique Ferrandon}, doi = {10.1038/embor.2011.238}, issn = {1469-3178}, year = {2012}, date = {2012-01-01}, journal = {EMBO Rep.}, volume = {13}, number = {1}, pages = {3--4}, keywords = {Animals, Cell Communication, Cell Transdifferentiation, ferrandon, Hematopoietic Stem Cells, Humans, Immune System, M3i, Signal Transduction, Stem Cell Niche}, pubstate = {published}, tppubtype = {article} } |
2011 |
Imler, Jean-Luc; Ferrandon, Dominique [Innate immunity crowned 2011 Nobel Prize winner] Article de journal Med Sci (Paris), 27 , p. 1019–24, 2011, ISSN: 0767-0974 (Print) 0767-0974 (Linking). Liens | BibTeX | Étiquettes: *Immunity, *Nobel Prize, Biological, ferrandon, Genetic Association Studies, Humans, imler, Immunotherapy/methods/trends, Innate/genetics, M3i, Models, Molecular Targeted Therapy/trends, Seasons, Structure-Activity Relationship, Toll-Like Receptors/chemistry/genetics/isolation & purification/physiology @article{imler_[innate_2011b, title = {[Innate immunity crowned 2011 Nobel Prize winner]}, author = {Jean-Luc Imler and Dominique Ferrandon}, url = {http://dx.doi.org.gate1.inist.fr/10.1051/medsci/20112711020}, doi = {10.1051/medsci/20112711020}, issn = {0767-0974 (Print) 0767-0974 (Linking)}, year = {2011}, date = {2011-11-01}, journal = {Med Sci (Paris)}, volume = {27}, pages = {1019--24}, keywords = {*Immunity, *Nobel Prize, Biological, ferrandon, Genetic Association Studies, Humans, imler, Immunotherapy/methods/trends, Innate/genetics, M3i, Models, Molecular Targeted Therapy/trends, Seasons, Structure-Activity Relationship, Toll-Like Receptors/chemistry/genetics/isolation & purification/physiology}, pubstate = {published}, tppubtype = {article} } |
Boyer, Laurent; Magoc, Lorin; Dejardin, Stephanie; Cappillino, Michael; Paquette, Nicholas; Hinault, Charlotte; Charriere, Guillaume M; Ip, Eddie W K; Fracchia, Shannon; Hennessy, Elizabeth; Erturk-Hasdemir, Deniz; Reichhart, Jean-Marc; Silverman, Neal; Lacy-Hulbert, Adam; Stuart, Lynda M Pathogen-derived effectors trigger protective immunity via activation of the Rac2 enzyme and the IMD or Rip kinase signaling pathway Article de journal Immunity, 35 (4), p. 536–549, 2011, ISSN: 1097-4180. Résumé | Liens | BibTeX | Étiquettes: Adaptor Proteins, Enzyme Activation, HEK293 Cells, Humans, M3i, rac GTP-Binding Proteins, Receptor-Interacting Protein Serine-Threonine Kinases, reichhart, Signal Transducing, Signal Transduction @article{boyer_pathogen-derived_2011, title = {Pathogen-derived effectors trigger protective immunity via activation of the Rac2 enzyme and the IMD or Rip kinase signaling pathway}, author = {Laurent Boyer and Lorin Magoc and Stephanie Dejardin and Michael Cappillino and Nicholas Paquette and Charlotte Hinault and Guillaume M Charriere and Eddie W K Ip and Shannon Fracchia and Elizabeth Hennessy and Deniz Erturk-Hasdemir and Jean-Marc Reichhart and Neal Silverman and Adam Lacy-Hulbert and Lynda M Stuart}, doi = {10.1016/j.immuni.2011.08.015}, issn = {1097-4180}, year = {2011}, date = {2011-10-01}, journal = {Immunity}, volume = {35}, number = {4}, pages = {536--549}, abstract = {Although infections with virulent pathogens often induce a strong inflammatory reaction, what drives the increased immune response to pathogens compared to nonpathogenic microbes is poorly understood. One possibility is that the immune system senses the level of threat from a microorganism and augments the response accordingly. Here, focusing on cytotoxic necrotizing factor 1 (CNF1), an Escherichia coli-derived effector molecule, we showed the host indirectly sensed the pathogen by monitoring for the effector that modified RhoGTPases. CNF1 modified Rac2, which then interacted with the innate immune adaptors IMD and Rip1-Rip2 in flies and mammalian cells, respectively, to drive an immune response. This response was protective and increased the ability of the host to restrict pathogen growth, thus defining a mechanism of effector-triggered immunity that contributes to how metazoans defend against microbes with pathogenic potential.}, keywords = {Adaptor Proteins, Enzyme Activation, HEK293 Cells, Humans, M3i, rac GTP-Binding Proteins, Receptor-Interacting Protein Serine-Threonine Kinases, reichhart, Signal Transducing, Signal Transduction}, pubstate = {published}, tppubtype = {article} } Although infections with virulent pathogens often induce a strong inflammatory reaction, what drives the increased immune response to pathogens compared to nonpathogenic microbes is poorly understood. One possibility is that the immune system senses the level of threat from a microorganism and augments the response accordingly. Here, focusing on cytotoxic necrotizing factor 1 (CNF1), an Escherichia coli-derived effector molecule, we showed the host indirectly sensed the pathogen by monitoring for the effector that modified RhoGTPases. CNF1 modified Rac2, which then interacted with the innate immune adaptors IMD and Rip1-Rip2 in flies and mammalian cells, respectively, to drive an immune response. This response was protective and increased the ability of the host to restrict pathogen growth, thus defining a mechanism of effector-triggered immunity that contributes to how metazoans defend against microbes with pathogenic potential. |
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. |
Limmer, Stefanie; Quintin, Jessica; Hetru, Charles; Ferrandon, Dominique Virulence on the fly: Drosophila melanogaster as a model genetic organism to decipher host-pathogen interactions Article de journal Curr Drug Targets, 12 (7), p. 978–999, 2011, ISSN: 1873-5592. Résumé | BibTeX | Étiquettes: Animal, Animals, Anti-Infective Agents, Disease Models, Drug Delivery Systems, Drug Design, Drug Resistance, ferrandon, Fungi, High-Throughput Screening Assays, Host-Pathogen Interactions, Humans, M3i, Microbial, Pseudomonas aeruginosa @article{limmer_virulence_2011b, title = {Virulence on the fly: Drosophila melanogaster as a model genetic organism to decipher host-pathogen interactions}, author = {Stefanie Limmer and Jessica Quintin and Charles Hetru and Dominique Ferrandon}, issn = {1873-5592}, year = {2011}, date = {2011-06-01}, journal = {Curr Drug Targets}, volume = {12}, number = {7}, pages = {978--999}, abstract = {To gain an in-depth grasp of infectious processes one has to know the specific interactions between the virulence factors of the pathogen and the host defense mechanisms. A thorough understanding is crucial for identifying potential new drug targets and designing drugs against which the pathogens might not develop resistance easily. Model organisms are a useful tool for this endeavor, thanks to the power of their genetics. Drosophila melanogaster is widely used to study host-pathogen interactions. Its basal immune response is well understood and is briefly reviewed here. Considerations relevant to choosing an adequate infection model are discussed. This review then focuses mainly on infections with two categories of pathogens, the well-studied Gram-negative bacterium Pseudomonas aeruginosa and infections by fungi of medical interest. These examples provide an overview over the current knowledge on Drosophila-pathogen interactions and illustrate the approaches that can be used to study those interactions. We also discuss the usefulness and limits of Drosophila infection models for studying specific host-pathogen interactions and high-throughput drug screening.}, keywords = {Animal, Animals, Anti-Infective Agents, Disease Models, Drug Delivery Systems, Drug Design, Drug Resistance, ferrandon, Fungi, High-Throughput Screening Assays, Host-Pathogen Interactions, Humans, M3i, Microbial, Pseudomonas aeruginosa}, pubstate = {published}, tppubtype = {article} } To gain an in-depth grasp of infectious processes one has to know the specific interactions between the virulence factors of the pathogen and the host defense mechanisms. A thorough understanding is crucial for identifying potential new drug targets and designing drugs against which the pathogens might not develop resistance easily. Model organisms are a useful tool for this endeavor, thanks to the power of their genetics. Drosophila melanogaster is widely used to study host-pathogen interactions. Its basal immune response is well understood and is briefly reviewed here. Considerations relevant to choosing an adequate infection model are discussed. This review then focuses mainly on infections with two categories of pathogens, the well-studied Gram-negative bacterium Pseudomonas aeruginosa and infections by fungi of medical interest. These examples provide an overview over the current knowledge on Drosophila-pathogen interactions and illustrate the approaches that can be used to study those interactions. We also discuss the usefulness and limits of Drosophila infection models for studying specific host-pathogen interactions and high-throughput drug screening. |
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. |
Whisstock, James C; Silverman, Gary A; Bird, Phillip I; Bottomley, Stephen P; Kaiserman, Dion; Luke, Cliff J; Pak, Stephen C; Reichhart, Jean-Marc; Huntington, James A Serpins flex their muscle: II. Structural insights into target peptidase recognition, polymerization, and transport functions Article de journal J. Biol. Chem., 285 (32), p. 24307–24312, 2010, ISSN: 1083-351X. Résumé | Liens | BibTeX | Étiquettes: Animals, Biological, Biological Transport, Biophysics, Catalytic Domain, Hormones, Humans, Kinetics, M3i, Models, Peptide Hydrolases, Protein Binding, Protein Conformation, Protein Structure, reichhart, Serpins, Substrate Specificity, Tertiary, Thrombin @article{whisstock_serpins_2010, title = {Serpins flex their muscle: II. Structural insights into target peptidase recognition, polymerization, and transport functions}, author = {James C Whisstock and Gary A Silverman and Phillip I Bird and Stephen P Bottomley and Dion Kaiserman and Cliff J Luke and Stephen C Pak and Jean-Marc Reichhart and James A Huntington}, doi = {10.1074/jbc.R110.141408}, issn = {1083-351X}, year = {2010}, date = {2010-08-01}, journal = {J. Biol. Chem.}, volume = {285}, number = {32}, pages = {24307--24312}, abstract = {Inhibitory serpins are metastable proteins that undergo a substantial conformational rearrangement to covalently trap target peptidases. The serpin reactive center loop contributes a majority of the interactions that serpins make during the initial binding to target peptidases. However, structural studies on serpin-peptidase complexes reveal a broader set of contacts on the scaffold of inhibitory serpins that have substantial influence on guiding peptidase recognition. Structural and biophysical studies also reveal how aberrant serpin folding can lead to the formation of domain-swapped serpin multimers rather than the monomeric metastable state. Serpin domain swapping may therefore underlie the polymerization events characteristic of the serpinopathies. Finally, recent structural studies reveal how the serpin fold has been adapted for non-inhibitory functions such as hormone binding.}, keywords = {Animals, Biological, Biological Transport, Biophysics, Catalytic Domain, Hormones, Humans, Kinetics, M3i, Models, Peptide Hydrolases, Protein Binding, Protein Conformation, Protein Structure, reichhart, Serpins, Substrate Specificity, Tertiary, Thrombin}, pubstate = {published}, tppubtype = {article} } Inhibitory serpins are metastable proteins that undergo a substantial conformational rearrangement to covalently trap target peptidases. The serpin reactive center loop contributes a majority of the interactions that serpins make during the initial binding to target peptidases. However, structural studies on serpin-peptidase complexes reveal a broader set of contacts on the scaffold of inhibitory serpins that have substantial influence on guiding peptidase recognition. Structural and biophysical studies also reveal how aberrant serpin folding can lead to the formation of domain-swapped serpin multimers rather than the monomeric metastable state. Serpin domain swapping may therefore underlie the polymerization events characteristic of the serpinopathies. Finally, recent structural studies reveal how the serpin fold has been adapted for non-inhibitory functions such as hormone binding. |
Garcia, Alvaro Baeza; Pierce, Raymond J; Gourbal, Benjamin; Werkmeister, Elisabeth; Colinet, Dominique; Reichhart, Jean-Marc; Dissous, Colette; Coustau, Christine Involvement of the cytokine MIF in the snail host immune response to the parasite Schistosoma mansoni Article de journal PLoS Pathog., 6 (9), p. e1001115, 2010, ISSN: 1553-7374. Résumé | Liens | BibTeX | Étiquettes: Amino Acid, Animals, Apoptosis, Biomphalaria, Blotting, Cell Proliferation, Cells, Cricetinae, Cultured, Hemocytes, Host-Parasite Interactions, Humans, Liver, M3i, Macrophage Migration-Inhibitory Factors, messenger, Oocysts, Recombinant Proteins, reichhart, Reverse Transcriptase Polymerase Chain Reaction, RNA, Schistosoma mansoni, Schistosomiasis mansoni, Sequence Homology, Small Interfering, Western @article{baeza_garcia_involvement_2010, title = {Involvement of the cytokine MIF in the snail host immune response to the parasite Schistosoma mansoni}, author = {Alvaro Baeza Garcia and Raymond J Pierce and Benjamin Gourbal and Elisabeth Werkmeister and Dominique Colinet and Jean-Marc Reichhart and Colette Dissous and Christine Coustau}, doi = {10.1371/journal.ppat.1001115}, issn = {1553-7374}, year = {2010}, date = {2010-01-01}, journal = {PLoS Pathog.}, volume = {6}, number = {9}, pages = {e1001115}, abstract = {We have identified and characterized a Macrophage Migration Inhibitory Factor (MIF) family member in the Lophotrochozoan invertebrate, Biomphalaria glabrata, the snail intermediate host of the human blood fluke Schistosoma mansoni. In mammals, MIF is a widely expressed pleiotropic cytokine with potent pro-inflammatory properties that controls cell functions such as gene expression, proliferation or apoptosis. Here we show that the MIF protein from B. glabrata (BgMIF) is expressed in circulating immune defense cells (hemocytes) of the snail as well as in the B. glabrata embryonic (Bge) cell line that has hemocyte-like features. Recombinant BgMIF (rBgMIF) induced cell proliferation and inhibited NO-dependent p53-mediated apoptosis in Bge cells. Moreover, knock-down of BgMIF expression in Bge cells interfered with the in vitro encapsulation of S. mansoni sporocysts. Furthermore, the in vivo knock-down of BgMIF prevented the changes in circulating hemocyte populations that occur in response to an infection by S. mansoni miracidia and led to a significant increase in the parasite burden of the snails. These results provide the first functional evidence that a MIF ortholog is involved in an invertebrate immune response towards a parasitic infection and highlight the importance of cytokines in invertebrate-parasite interactions.}, keywords = {Amino Acid, Animals, Apoptosis, Biomphalaria, Blotting, Cell Proliferation, Cells, Cricetinae, Cultured, Hemocytes, Host-Parasite Interactions, Humans, Liver, M3i, Macrophage Migration-Inhibitory Factors, messenger, Oocysts, Recombinant Proteins, reichhart, Reverse Transcriptase Polymerase Chain Reaction, RNA, Schistosoma mansoni, Schistosomiasis mansoni, Sequence Homology, Small Interfering, Western}, pubstate = {published}, tppubtype = {article} } We have identified and characterized a Macrophage Migration Inhibitory Factor (MIF) family member in the Lophotrochozoan invertebrate, Biomphalaria glabrata, the snail intermediate host of the human blood fluke Schistosoma mansoni. In mammals, MIF is a widely expressed pleiotropic cytokine with potent pro-inflammatory properties that controls cell functions such as gene expression, proliferation or apoptosis. Here we show that the MIF protein from B. glabrata (BgMIF) is expressed in circulating immune defense cells (hemocytes) of the snail as well as in the B. glabrata embryonic (Bge) cell line that has hemocyte-like features. Recombinant BgMIF (rBgMIF) induced cell proliferation and inhibited NO-dependent p53-mediated apoptosis in Bge cells. Moreover, knock-down of BgMIF expression in Bge cells interfered with the in vitro encapsulation of S. mansoni sporocysts. Furthermore, the in vivo knock-down of BgMIF prevented the changes in circulating hemocyte populations that occur in response to an infection by S. mansoni miracidia and led to a significant increase in the parasite burden of the snails. These results provide the first functional evidence that a MIF ortholog is involved in an invertebrate immune response towards a parasitic infection and highlight the importance of cytokines in invertebrate-parasite interactions. |
Pospisilik, Andrew J; Schramek, Daniel; Schnidar, Harald; Cronin, Shane J F; Nehme, Nadine T; Zhang, Xiaoyun; Knauf, Claude; Cani, Patrice D; Aumayr, Karin; Todoric, Jelena; Bayer, Martina; Haschemi, Arvand; Puviindran, Vijitha; Tar, Krisztina; Orthofer, Michael; Neely, Gregory G; Dietzl, Georg; Manoukian, Armen; Funovics, Martin; Prager, Gerhard; Wagner, Oswald; Ferrandon, Dominique; Aberger, Fritz; Hui, Chi-chung; Esterbauer, Harald; Penninger, Josef M Drosophila genome-wide obesity screen reveals hedgehog as a determinant of brown versus white adipose cell fate Article de journal Cell, 140 (1), p. 148–160, 2010, ISSN: 1097-4172. Résumé | Liens | BibTeX | Étiquettes: Adipocytes, Adipogenesis, Animals, Brown, Brown/metabolism, Cyclic AMP, Cyclic AMP/metabolism, Drosophila Proteins/*metabolism, ferrandon, Glucocorticoids, Glucocorticoids/metabolism, Hedgehog Proteins, Hedgehog Proteins/*metabolism, Humans, Knockout, M3i, Mice, Muscle Cells, Muscle Cells/metabolism, Obesity, Obesity/*genetics, Repressor Proteins, Repressor Proteins/genetics, White, White/metabolism @article{pospisilik_drosophila_2010b, title = {Drosophila genome-wide obesity screen reveals hedgehog as a determinant of brown versus white adipose cell fate}, author = {Andrew J Pospisilik and Daniel Schramek and Harald Schnidar and Shane J F Cronin and Nadine T Nehme and Xiaoyun Zhang and Claude Knauf and Patrice D Cani and Karin Aumayr and Jelena Todoric and Martina Bayer and Arvand Haschemi and Vijitha Puviindran and Krisztina Tar and Michael Orthofer and Gregory G Neely and Georg Dietzl and Armen Manoukian and Martin Funovics and Gerhard Prager and Oswald Wagner and Dominique Ferrandon and Fritz Aberger and Chi-chung Hui and Harald Esterbauer and Josef M Penninger}, doi = {10.1016/j.cell.2009.12.027}, issn = {1097-4172}, year = {2010}, date = {2010-01-01}, journal = {Cell}, volume = {140}, number = {1}, pages = {148--160}, abstract = {Over 1 billion people are estimated to be overweight, placing them at risk for diabetes, cardiovascular disease, and cancer. We performed a systems-level genetic dissection of adiposity regulation using genome-wide RNAi screening in adult Drosophila. As a follow-up, the resulting approximately 500 candidate obesity genes were functionally classified using muscle-, oenocyte-, fat-body-, and neuronal-specific knockdown in vivo and revealed hedgehog signaling as the top-scoring fat-body-specific pathway. To extrapolate these findings into mammals, we generated fat-specific hedgehog-activation mutant mice. Intriguingly, these mice displayed near total loss of white, but not brown, fat compartments. Mechanistically, activation of hedgehog signaling irreversibly blocked differentiation of white adipocytes through direct, coordinate modulation of early adipogenic factors. These findings identify a role for hedgehog signaling in white/brown adipocyte determination and link in vivo RNAi-based scanning of the Drosophila genome to regulation of adipocyte cell fate in mammals.}, keywords = {Adipocytes, Adipogenesis, Animals, Brown, Brown/metabolism, Cyclic AMP, Cyclic AMP/metabolism, Drosophila Proteins/*metabolism, ferrandon, Glucocorticoids, Glucocorticoids/metabolism, Hedgehog Proteins, Hedgehog Proteins/*metabolism, Humans, Knockout, M3i, Mice, Muscle Cells, Muscle Cells/metabolism, Obesity, Obesity/*genetics, Repressor Proteins, Repressor Proteins/genetics, White, White/metabolism}, pubstate = {published}, tppubtype = {article} } Over 1 billion people are estimated to be overweight, placing them at risk for diabetes, cardiovascular disease, and cancer. We performed a systems-level genetic dissection of adiposity regulation using genome-wide RNAi screening in adult Drosophila. As a follow-up, the resulting approximately 500 candidate obesity genes were functionally classified using muscle-, oenocyte-, fat-body-, and neuronal-specific knockdown in vivo and revealed hedgehog signaling as the top-scoring fat-body-specific pathway. To extrapolate these findings into mammals, we generated fat-specific hedgehog-activation mutant mice. Intriguingly, these mice displayed near total loss of white, but not brown, fat compartments. Mechanistically, activation of hedgehog signaling irreversibly blocked differentiation of white adipocytes through direct, coordinate modulation of early adipogenic factors. These findings identify a role for hedgehog signaling in white/brown adipocyte determination and link in vivo RNAi-based scanning of the Drosophila genome to regulation of adipocyte cell fate in mammals. |
2009 |
Kondo, J [Exploring the "motion" = "function" of the ribosomal A-site molecular switch] Article de journal Tanpakushitsu Kakusan Koso, 54 (11), p. 1356-62, 2009, (0039-9450 (Print) 0039-9450 (Linking) Journal Article Review). BibTeX | Étiquettes: *Binding, *RNA/genetics, Agents/adverse, Anti-Bacterial, Bacteria/drug, Biosynthesis/genetics, Crystallography, Disorders/genetics, effects, effects/pharmacology, Hearing, Humans, Mutation, Protein, Ribosomes/chemistry/*genetics/*physiology, RNA, Sites, Transfer, Untranslated, WESTHOF, X-Ray @article{, title = {[Exploring the "motion" = "function" of the ribosomal A-site molecular switch]}, author = { J. Kondo}, year = {2009}, date = {2009-01-01}, journal = {Tanpakushitsu Kakusan Koso}, volume = {54}, number = {11}, pages = {1356-62}, note = {0039-9450 (Print) 0039-9450 (Linking) Journal Article Review}, keywords = {*Binding, *RNA/genetics, Agents/adverse, Anti-Bacterial, Bacteria/drug, Biosynthesis/genetics, Crystallography, Disorders/genetics, effects, effects/pharmacology, Hearing, Humans, Mutation, Protein, Ribosomes/chemistry/*genetics/*physiology, RNA, Sites, Transfer, Untranslated, WESTHOF, X-Ray}, pubstate = {published}, tppubtype = {article} } |
2008 |
Deddouche, Safia; Matt, Nicolas; Budd, Aidan; Mueller, Stefanie; Kemp, Cordula; Galiana-Arnoux, Delphine; Dostert, Catherine; Antoniewski, Christophe; Hoffmann, Jules A; Imler, Jean-Luc The DExD/Ħ-box helicase Dicer-2 mediates the induction of antiviral activity in drosophila Article de journal Nature Immunology, 9 (12), p. 1425–1432, 2008, ISSN: 1529-2916. Résumé | Liens | BibTeX | Étiquettes: Amino Acid, Animals, Electrophoresis, Fat Body, Gene Expression Regulation, Genetic, Genetically Modified, hoffmann, Humans, imler, M3i, matt, Phylogeny, Polyacrylamide Gel, Reverse Transcriptase Polymerase Chain Reaction, Ribonuclease III, RNA Helicases, Sequence Homology, Transcription, Virus Diseases @article{deddouche_dexd/h-box_2008, title = {The DExD/Ħ-box helicase Dicer-2 mediates the induction of antiviral activity in drosophila}, author = {Safia Deddouche and Nicolas Matt and Aidan Budd and Stefanie Mueller and Cordula Kemp and Delphine Galiana-Arnoux and Catherine Dostert and Christophe Antoniewski and Jules A Hoffmann and Jean-Luc Imler}, doi = {10.1038/ni.1664}, issn = {1529-2916}, year = {2008}, date = {2008-12-01}, journal = {Nature Immunology}, volume = {9}, number = {12}, pages = {1425--1432}, abstract = {Drosophila, like other invertebrates and plants, relies mainly on RNA interference for its defense against viruses. In flies, viral infection also triggers the expression of many genes. One of the genes induced, Vago, encodes a 18-kilodalton cysteine-rich polypeptide. Here we provide genetic evidence that the Vago gene product controlled viral load in the fat body after infection with drosophila C virus. Induction of Vago was dependent on the helicase Dicer-2. Dicer-2 belongs to the same DExD/H-box helicase family as do the RIG-I-like receptors, which sense viral infection and mediate interferon induction in mammals. We propose that this family represents an evolutionary conserved set of sensors that detect viral nucleic acids and direct antiviral responses.}, keywords = {Amino Acid, Animals, Electrophoresis, Fat Body, Gene Expression Regulation, Genetic, Genetically Modified, hoffmann, Humans, imler, M3i, matt, Phylogeny, Polyacrylamide Gel, Reverse Transcriptase Polymerase Chain Reaction, Ribonuclease III, RNA Helicases, Sequence Homology, Transcription, Virus Diseases}, pubstate = {published}, tppubtype = {article} } Drosophila, like other invertebrates and plants, relies mainly on RNA interference for its defense against viruses. In flies, viral infection also triggers the expression of many genes. One of the genes induced, Vago, encodes a 18-kilodalton cysteine-rich polypeptide. Here we provide genetic evidence that the Vago gene product controlled viral load in the fat body after infection with drosophila C virus. Induction of Vago was dependent on the helicase Dicer-2. Dicer-2 belongs to the same DExD/H-box helicase family as do the RIG-I-like receptors, which sense viral infection and mediate interferon induction in mammals. We propose that this family represents an evolutionary conserved set of sensors that detect viral nucleic acids and direct antiviral responses. |
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. |
Roetzer, Andreas; Gregori, Christa; Jennings, Ann Marie; Quintin, Jessica; Ferrandon, Dominique; Butler, Geraldine; Kuchler, Karl; Ammerer, Gustav; Schüller, Christoph Candida glabrata environmental stress response involves Saccharomyces cerevisiae Msn2/4 orthologous transcription factors Article de journal Mol. Microbiol., 69 (3), p. 603–620, 2008, ISSN: 1365-2958. Résumé | Liens | BibTeX | Étiquettes: Animals, Candida glabrata, Candidiasis, DNA-Binding Proteins, ferrandon, Fungal, Fungal Proteins, Gene Expression Profiling, Gene Expression Regulation, Genetic, Humans, M3i, Oligonucleotide Array Sequence Analysis, Osmotic Pressure, Regulon, Saccharomyces cerevisiae Proteins, Transcription, Transcription Factors, Virulence, Yeasts @article{roetzer_candida_2008b, title = {Candida glabrata environmental stress response involves Saccharomyces cerevisiae Msn2/4 orthologous transcription factors}, author = {Andreas Roetzer and Christa Gregori and Ann Marie Jennings and Jessica Quintin and Dominique Ferrandon and Geraldine Butler and Karl Kuchler and Gustav Ammerer and Christoph Schüller}, doi = {10.1111/j.1365-2958.2008.06301.x}, issn = {1365-2958}, year = {2008}, date = {2008-01-01}, journal = {Mol. Microbiol.}, volume = {69}, number = {3}, pages = {603--620}, abstract = {We determined the genome-wide environmental stress response (ESR) expression profile of Candida glabrata, a human pathogen related to Saccharomyces cerevisiae. Despite different habitats, C. glabrata, S. cerevisiae, Schizosaccharomyces pombe and Candida albicans have a qualitatively similar ESR. We investigate the function of the C. glabrata syntenic orthologues to the ESR transcription factor Msn2. The C. glabrata orthologues CgMsn2 and CgMsn4 contain a motif previously referred to as HD1 (homology domain 1) also present in Msn2 orthologues from fungi closely related to S. cerevisiae. We show that regions including this motif confer stress-regulated intracellular localization when expressed in S. cerevisiae. Site-directed mutagenesis confirms that nuclear export of CgMsn2 in C. glabrata requires an intact HD1. Transcript profiles of CgMsn2/4 mutants and CgMsn2 overexpression strains show that they regulate a part of the CgESR. CgMsn2 complements a S. cerevisiae msn2 null mutant and in stressed C. glabrata cells, rapidly translocates from the cytosol to the nucleus. CgMsn2 is required for full resistance against severe osmotic stress and rapid and full induction of trehalose synthesis genes (TPS1, TPS2). Constitutive activation of CgMsn2 is detrimental for C. glabrata. These results establish an Msn2-regulated general stress response in C. glabrata.}, keywords = {Animals, Candida glabrata, Candidiasis, DNA-Binding Proteins, ferrandon, Fungal, Fungal Proteins, Gene Expression Profiling, Gene Expression Regulation, Genetic, Humans, M3i, Oligonucleotide Array Sequence Analysis, Osmotic Pressure, Regulon, Saccharomyces cerevisiae Proteins, Transcription, Transcription Factors, Virulence, Yeasts}, pubstate = {published}, tppubtype = {article} } We determined the genome-wide environmental stress response (ESR) expression profile of Candida glabrata, a human pathogen related to Saccharomyces cerevisiae. Despite different habitats, C. glabrata, S. cerevisiae, Schizosaccharomyces pombe and Candida albicans have a qualitatively similar ESR. We investigate the function of the C. glabrata syntenic orthologues to the ESR transcription factor Msn2. The C. glabrata orthologues CgMsn2 and CgMsn4 contain a motif previously referred to as HD1 (homology domain 1) also present in Msn2 orthologues from fungi closely related to S. cerevisiae. We show that regions including this motif confer stress-regulated intracellular localization when expressed in S. cerevisiae. Site-directed mutagenesis confirms that nuclear export of CgMsn2 in C. glabrata requires an intact HD1. Transcript profiles of CgMsn2/4 mutants and CgMsn2 overexpression strains show that they regulate a part of the CgESR. CgMsn2 complements a S. cerevisiae msn2 null mutant and in stressed C. glabrata cells, rapidly translocates from the cytosol to the nucleus. CgMsn2 is required for full resistance against severe osmotic stress and rapid and full induction of trehalose synthesis genes (TPS1, TPS2). Constitutive activation of CgMsn2 is detrimental for C. glabrata. These results establish an Msn2-regulated general stress response in C. glabrata. |
2007 |
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. |
Ferrandon, Dominique; Gottar, Marie; Gobert, Vanessa [New mechanism for detection of infections using the innate immune system of animals] Article de journal Med Sci (Paris), 23 (8-9), p. 707–709, 2007, ISSN: 0767-0974. Liens | BibTeX | Étiquettes: Animal, Animals, Drosophila/immunology, ferrandon, Gram-Positive Bacteria, Gram-Positive Bacteria/pathogenicity, Gram-Positive Bacterial Infections, Gram-Positive Bacterial Infections/immunology, Humans, Immune System, infection, Infection/*diagnosis/*immunology, M3i, Models @article{ferrandon_[new_2007b, title = {[New mechanism for detection of infections using the innate immune system of animals]}, author = {Dominique Ferrandon and Marie Gottar and Vanessa Gobert}, doi = {10.1051/medsci/20072389707}, issn = {0767-0974}, year = {2007}, date = {2007-09-01}, journal = {Med Sci (Paris)}, volume = {23}, number = {8-9}, pages = {707--709}, keywords = {Animal, Animals, Drosophila/immunology, ferrandon, Gram-Positive Bacteria, Gram-Positive Bacteria/pathogenicity, Gram-Positive Bacterial Infections, Gram-Positive Bacterial Infections/immunology, Humans, Immune System, infection, Infection/*diagnosis/*immunology, M3i, Models}, pubstate = {published}, tppubtype = {article} } |
2006 |
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 |
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. |
Weber, Alexander N R; Moncrieffe, Martin C; Gangloff, Monique; Imler, Jean-Luc; Gay, Nicholas J Ligand-receptor and receptor-receptor interactions act in concert to activate signaling in the Drosophila toll pathway Article de journal The Journal of Biological Chemistry, 280 (24), p. 22793–22799, 2005, ISSN: 0021-9258. Résumé | Liens | BibTeX | Étiquettes: Amino Acid, Animals, Biophysical Phenomena, Biophysics, Body Patterning, Calorimetry, Cell Line, Cell Surface, Cross-Linking Reagents, Cytokines, dimerization, Electrophoresis, Humans, imler, ligands, Luciferases, M3i, Membrane Glycoproteins, Polyacrylamide Gel, Protein Binding, Protein Structure, Receptors, Recombinant Proteins, Sequence Homology, Signal Transduction, Tertiary, Time Factors, Toll-Like Receptors, Ultracentrifugation @article{weber_ligand-receptor_2005, title = {Ligand-receptor and receptor-receptor interactions act in concert to activate signaling in the Drosophila toll pathway}, author = {Alexander N R Weber and Martin C Moncrieffe and Monique Gangloff and Jean-Luc Imler and Nicholas J Gay}, doi = {10.1074/jbc.M502074200}, issn = {0021-9258}, year = {2005}, date = {2005-01-01}, journal = {The Journal of Biological Chemistry}, volume = {280}, number = {24}, pages = {22793--22799}, abstract = {In Drosophila, the signaling pathway mediated by the Toll receptor is critical for the establishment of embryonic dorso-ventral pattern and for innate immune responses to bacterial and fungal pathogens. Toll is activated by high affinity binding of the cytokine Spätzle, a dimeric ligand of the cystine knot family. In vertebrates, a related family of Toll-like receptors play a critical role in innate immune responses. Despite the importance of this family of receptors, little is known about the biochemical events that lead to receptor activation and signaling. Here, we show that Spätzle binds to the N-terminal region of Toll and, using biophysical methods, that the binding is complex. The two binding events that cause formation of the cross-linked complex are non-equivalent: the first Toll ectodomain binds Spätzle with an affinity 3-fold higher than the second molecule suggesting that pathway activation involves negative cooperativity. We further show that the Toll ectodomains are able to form low affinity dimers in solution and that juxtamembrane sequences of Toll are critical for the activation or derepression of the pathway. These results, taken together, suggest a mechanism of signal transduction that requires both ligand-receptor and receptor-receptor interactions.}, keywords = {Amino Acid, Animals, Biophysical Phenomena, Biophysics, Body Patterning, Calorimetry, Cell Line, Cell Surface, Cross-Linking Reagents, Cytokines, dimerization, Electrophoresis, Humans, imler, ligands, Luciferases, M3i, Membrane Glycoproteins, Polyacrylamide Gel, Protein Binding, Protein Structure, Receptors, Recombinant Proteins, Sequence Homology, Signal Transduction, Tertiary, Time Factors, Toll-Like Receptors, Ultracentrifugation}, pubstate = {published}, tppubtype = {article} } In Drosophila, the signaling pathway mediated by the Toll receptor is critical for the establishment of embryonic dorso-ventral pattern and for innate immune responses to bacterial and fungal pathogens. Toll is activated by high affinity binding of the cytokine Spätzle, a dimeric ligand of the cystine knot family. In vertebrates, a related family of Toll-like receptors play a critical role in innate immune responses. Despite the importance of this family of receptors, little is known about the biochemical events that lead to receptor activation and signaling. Here, we show that Spätzle binds to the N-terminal region of Toll and, using biophysical methods, that the binding is complex. The two binding events that cause formation of the cross-linked complex are non-equivalent: the first Toll ectodomain binds Spätzle with an affinity 3-fold higher than the second molecule suggesting that pathway activation involves negative cooperativity. We further show that the Toll ectodomains are able to form low affinity dimers in solution and that juxtamembrane sequences of Toll are critical for the activation or derepression of the pathway. These results, taken together, suggest a mechanism of signal transduction that requires both ligand-receptor and receptor-receptor interactions. |
2004 |
Imler, Jean-Luc; Zheng, Liangbiao Biology of Toll receptors: lessons from insects and mammals Article de journal Journal of Leukocyte Biology, 75 (1), p. 18–26, 2004, ISSN: 0741-5400. Résumé | Liens | BibTeX | Étiquettes: Animals, Anopheles, Cell Surface, Humans, imler, M3i, Membrane Glycoproteins, Mice, Phylogeny, Plant Physiological Phenomena, Receptors, Signal Transduction, Toll-Like Receptor 5, Toll-Like Receptors @article{imler_biology_2004, title = {Biology of Toll receptors: lessons from insects and mammals}, author = {Jean-Luc Imler and Liangbiao Zheng}, doi = {10.1189/jlb.0403160}, issn = {0741-5400}, year = {2004}, date = {2004-01-01}, journal = {Journal of Leukocyte Biology}, volume = {75}, number = {1}, pages = {18--26}, abstract = {Toll receptors are type I transmembrane proteins that play important roles in development and immunity in animals. Comparison of the genomes of mouse and human on one side and of the fruitfly Drosophila and the mosquito Anopheles (two dipteran insects) on the other, revealed that the four species possess a similar number of Toll receptors (approximately 10). However, phylogenetic analyses indicate that the families of Toll receptors expanded independently in insects and mammals. We review recent results on these receptors, which point to differences in the activation and signaling between Tolls in insects and Toll-like receptors (TLRs) in mammals. Whereas mammalian TLRs appear to be solely dedicated to host-defense, insect Tolls may be predominantly linked to other functions, probably developmental.}, keywords = {Animals, Anopheles, Cell Surface, Humans, imler, M3i, Membrane Glycoproteins, Mice, Phylogeny, Plant Physiological Phenomena, Receptors, Signal Transduction, Toll-Like Receptor 5, Toll-Like Receptors}, pubstate = {published}, tppubtype = {article} } Toll receptors are type I transmembrane proteins that play important roles in development and immunity in animals. Comparison of the genomes of mouse and human on one side and of the fruitfly Drosophila and the mosquito Anopheles (two dipteran insects) on the other, revealed that the four species possess a similar number of Toll receptors (approximately 10). However, phylogenetic analyses indicate that the families of Toll receptors expanded independently in insects and mammals. We review recent results on these receptors, which point to differences in the activation and signaling between Tolls in insects and Toll-like receptors (TLRs) in mammals. Whereas mammalian TLRs appear to be solely dedicated to host-defense, insect Tolls may be predominantly linked to other functions, probably developmental. |
Blandin, Stephanie A; Shiao, Shin-Hong; Moita, Luis F; Janse, Chris J; Waters, Andrew P; Kafatos, Fotis C; Levashina, Elena A Complement-like protein TEP1 is a determinant of vectorial capacity in the malaria vector Anopheles gambiae Article de journal Cell, 116 (5), p. 661–670, 2004, ISSN: 0092-8674. Résumé | BibTeX | Étiquettes: Animals, Anopheles, blandin, Female, Genetic, Humans, Insect Proteins, Insect Vectors, M3i, Malaria, Models, Molecular, Plasmodium berghei, Polymorphism, Protein Structure, RNA, Sequence Alignment, Tertiary @article{blandin_complement-like_2004, title = {Complement-like protein TEP1 is a determinant of vectorial capacity in the malaria vector Anopheles gambiae}, author = {Stephanie A Blandin and Shin-Hong Shiao and Luis F Moita and Chris J Janse and Andrew P Waters and Fotis C Kafatos and Elena A Levashina}, issn = {0092-8674}, year = {2004}, date = {2004-01-01}, journal = {Cell}, volume = {116}, number = {5}, pages = {661--670}, abstract = {Anopheles mosquitoes are major vectors of human malaria in Africa. Large variation exists in the ability of mosquitoes to serve as vectors and to transmit malaria parasites, but the molecular mechanisms that determine vectorial capacity remain poorly understood. We report that the hemocyte-specific complement-like protein TEP1 from the mosquito Anopheles gambiae binds to and mediates killing of midgut stages of the rodent malaria parasite Plasmodium berghei. The dsRNA knockdown of TEP1 in adults completely abolishes melanotic refractoriness in a genetically selected refractory strain. Moreover, in susceptible mosquitoes this knockdown increases the number of developing parasites. Our results suggest that the TEP1-dependent parasite killing is followed by a TEP1-independent clearance of dead parasites by lysis and/or melanization. Further elucidation of the molecular mechanisms of TEP1-mediated parasite killing will be of great importance for our understanding of the principles of vectorial capacity in insects.}, keywords = {Animals, Anopheles, blandin, Female, Genetic, Humans, Insect Proteins, Insect Vectors, M3i, Malaria, Models, Molecular, Plasmodium berghei, Polymorphism, Protein Structure, RNA, Sequence Alignment, Tertiary}, pubstate = {published}, tppubtype = {article} } Anopheles mosquitoes are major vectors of human malaria in Africa. Large variation exists in the ability of mosquitoes to serve as vectors and to transmit malaria parasites, but the molecular mechanisms that determine vectorial capacity remain poorly understood. We report that the hemocyte-specific complement-like protein TEP1 from the mosquito Anopheles gambiae binds to and mediates killing of midgut stages of the rodent malaria parasite Plasmodium berghei. The dsRNA knockdown of TEP1 in adults completely abolishes melanotic refractoriness in a genetically selected refractory strain. Moreover, in susceptible mosquitoes this knockdown increases the number of developing parasites. Our results suggest that the TEP1-dependent parasite killing is followed by a TEP1-independent clearance of dead parasites by lysis and/or melanization. Further elucidation of the molecular mechanisms of TEP1-mediated parasite killing will be of great importance for our understanding of the principles of vectorial capacity in insects. |
2003 |
Reichhart, Jean-Marc TLR5 takes aim at bacterial propeller Article de journal Nat. Immunol., 4 (12), p. 1159–1160, 2003, ISSN: 1529-2908. Liens | BibTeX | Étiquettes: Animals, Bacterial Physiological Phenomena, Cell Surface, Flagella, Flagellin, Humans, M3i, Membrane Glycoproteins, Receptors, reichhart, Toll-Like Receptor 5, Toll-Like Receptors @article{reichhart_tlr5_2003, title = {TLR5 takes aim at bacterial propeller}, author = {Jean-Marc Reichhart}, doi = {10.1038/ni1203-1159}, issn = {1529-2908}, year = {2003}, date = {2003-12-01}, journal = {Nat. Immunol.}, volume = {4}, number = {12}, pages = {1159--1160}, keywords = {Animals, Bacterial Physiological Phenomena, Cell Surface, Flagella, Flagellin, Humans, M3i, Membrane Glycoproteins, Receptors, reichhart, Toll-Like Receptor 5, Toll-Like Receptors}, pubstate = {published}, tppubtype = {article} } |
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. |
Green, Clare; Brown, Gemma; Dafforn, Timothy R; Reichhart, Jean-Marc; Morley, Terri; Lomas, David A; Gubb, David Drosophila necrotic mutations mirror disease-associated variants of human serpins Article de journal Development, 130 (7), p. 1473–1478, 2003, ISSN: 0950-1991. Résumé | BibTeX | Étiquettes: Animals, Humans, M3i, Necrosis, reichhart, Serpins, Temperature, Urea @article{green_drosophila_2003, title = {Drosophila necrotic mutations mirror disease-associated variants of human serpins}, author = {Clare Green and Gemma Brown and Timothy R Dafforn and Jean-Marc Reichhart and Terri Morley and David A Lomas and David Gubb}, issn = {0950-1991}, year = {2003}, date = {2003-04-01}, journal = {Development}, volume = {130}, number = {7}, pages = {1473--1478}, abstract = {Polymerization of members of the serpin superfamily underlies diseases as diverse as cirrhosis, angioedema, thrombosis and dementia. The Drosophila serpin Necrotic controls the innate immune response and is homologous to human alpha(1)-antitrypsin. We show that necrotic mutations that are identical to the Z-deficiency variant of alpha(1)-antitrypsin form urea-stable polymers in vivo. These necrotic mutations are temperature sensitive, which is in keeping with the temperature-dependent polymerization of serpins in vitro and the role of childhood fevers in exacerbating liver disease in Z alpha-antitrypsin deficiency. In addition, we identify two nec mutations homologous to an antithrombin point mutation that is responsible for neonatal thrombosis. Transgenic flies carrying an StextgreaterF amino-acid substitution equivalent to that found in Siiyama-variant antitrypsin (nec(StextgreaterF.UAS)) fail to complement nec-null mutations and demonstrate a dominant temperature-dependent inactivation of the wild-type nec allele. Taken together, these data establish Drosophila as a powerful system to study serpin polymerization in vivo.}, keywords = {Animals, Humans, M3i, Necrosis, reichhart, Serpins, Temperature, Urea}, pubstate = {published}, tppubtype = {article} } Polymerization of members of the serpin superfamily underlies diseases as diverse as cirrhosis, angioedema, thrombosis and dementia. The Drosophila serpin Necrotic controls the innate immune response and is homologous to human alpha(1)-antitrypsin. We show that necrotic mutations that are identical to the Z-deficiency variant of alpha(1)-antitrypsin form urea-stable polymers in vivo. These necrotic mutations are temperature sensitive, which is in keeping with the temperature-dependent polymerization of serpins in vitro and the role of childhood fevers in exacerbating liver disease in Z alpha-antitrypsin deficiency. In addition, we identify two nec mutations homologous to an antithrombin point mutation that is responsible for neonatal thrombosis. Transgenic flies carrying an StextgreaterF amino-acid substitution equivalent to that found in Siiyama-variant antitrypsin (nec(StextgreaterF.UAS)) fail to complement nec-null mutations and demonstrate a dominant temperature-dependent inactivation of the wild-type nec allele. Taken together, these data establish Drosophila as a powerful system to study serpin polymerization in vivo. |
Imler, Jean-Luc; Hoffmann, Jules A Toll signaling: the TIReless quest for specificity Article de journal Nature Immunology, 4 (2), p. 105–106, 2003, ISSN: 1529-2908. Liens | BibTeX | Étiquettes: Animals, Cell Surface, Dendritic Cells, hoffmann, Humans, imler, Immunological, Interferon-beta, M3i, Membrane Glycoproteins, Mice, Models, Protein Structure, Receptors, Signal Transduction, Tertiary, Toll-Like Receptors @article{imler_toll_2003, title = {Toll signaling: the TIReless quest for specificity}, author = {Jean-Luc Imler and Jules A Hoffmann}, doi = {10.1038/ni0203-105}, issn = {1529-2908}, year = {2003}, date = {2003-02-01}, journal = {Nature Immunology}, volume = {4}, number = {2}, pages = {105--106}, keywords = {Animals, Cell Surface, Dendritic Cells, hoffmann, Humans, imler, Immunological, Interferon-beta, M3i, Membrane Glycoproteins, Mice, Models, Protein Structure, Receptors, Signal Transduction, Tertiary, Toll-Like Receptors}, pubstate = {published}, tppubtype = {article} } |
2001 |
Michel, T; Reichhart, Jean-Marc; Hoffmann, Jules A; Royet, Julien Drosophila Toll is activated by Gram-positive bacteria through a circulating peptidoglycan recognition protein Article de journal Nature, 414 (6865), p. 756–759, 2001, ISSN: 0028-0836. Résumé | Liens | BibTeX | Étiquettes: Amino Acid, Animals, Anti-Bacterial Agents, Anti-Infective Agents, Bacillus thuringiensis, Carrier Proteins, Cell Surface, Chromosome Mapping, Enterococcus faecalis, Fungi, Genes, Gram-Positive Bacteria, Hemolymph, hoffmann, Humans, Insect, Insect Proteins, M3i, Membrane Glycoproteins, Micrococcus luteus, Mutation, Receptors, reichhart, Sequence Homology, Toll-Like Receptors @article{michel_drosophila_2001, title = {Drosophila Toll is activated by Gram-positive bacteria through a circulating peptidoglycan recognition protein}, author = {T Michel and Jean-Marc Reichhart and Jules A Hoffmann and Julien Royet}, doi = {10.1038/414756a}, issn = {0028-0836}, year = {2001}, date = {2001-12-01}, journal = {Nature}, volume = {414}, number = {6865}, pages = {756--759}, abstract = {Microbial infection activates two distinct intracellular signalling cascades in the immune-responsive fat body of Drosophila. Gram-positive bacteria and fungi predominantly induce the Toll signalling pathway, whereas Gram-negative bacteria activate the Imd pathway. Loss-of-function mutants in either pathway reduce the resistance to corresponding infections. Genetic screens have identified a range of genes involved in these intracellular signalling cascades, but how they are activated by microbial infection is largely unknown. Activation of the transmembrane receptor Toll requires a proteolytically cleaved form of an extracellular cytokine-like polypeptide, Spätzle, suggesting that Toll does not itself function as a bona fide recognition receptor of microbial patterns. This is in apparent contrast with the mammalian Toll-like receptors and raises the question of which host molecules actually recognize microbial patterns to activate Toll through Spätzle. Here we present a mutation that blocks Toll activation by Gram-positive bacteria and significantly decreases resistance to this type of infection. The mutation semmelweis (seml) inactivates the gene encoding a peptidoglycan recognition protein (PGRP-SA). Interestingly, seml does not affect Toll activation by fungal infection, indicating the existence of a distinct recognition system for fungi to activate the Toll pathway.}, keywords = {Amino Acid, Animals, Anti-Bacterial Agents, Anti-Infective Agents, Bacillus thuringiensis, Carrier Proteins, Cell Surface, Chromosome Mapping, Enterococcus faecalis, Fungi, Genes, Gram-Positive Bacteria, Hemolymph, hoffmann, Humans, Insect, Insect Proteins, M3i, Membrane Glycoproteins, Micrococcus luteus, Mutation, Receptors, reichhart, Sequence Homology, Toll-Like Receptors}, pubstate = {published}, tppubtype = {article} } Microbial infection activates two distinct intracellular signalling cascades in the immune-responsive fat body of Drosophila. Gram-positive bacteria and fungi predominantly induce the Toll signalling pathway, whereas Gram-negative bacteria activate the Imd pathway. Loss-of-function mutants in either pathway reduce the resistance to corresponding infections. Genetic screens have identified a range of genes involved in these intracellular signalling cascades, but how they are activated by microbial infection is largely unknown. Activation of the transmembrane receptor Toll requires a proteolytically cleaved form of an extracellular cytokine-like polypeptide, Spätzle, suggesting that Toll does not itself function as a bona fide recognition receptor of microbial patterns. This is in apparent contrast with the mammalian Toll-like receptors and raises the question of which host molecules actually recognize microbial patterns to activate Toll through Spätzle. Here we present a mutation that blocks Toll activation by Gram-positive bacteria and significantly decreases resistance to this type of infection. The mutation semmelweis (seml) inactivates the gene encoding a peptidoglycan recognition protein (PGRP-SA). Interestingly, seml does not affect Toll activation by fungal infection, indicating the existence of a distinct recognition system for fungi to activate the Toll pathway. |
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. |
1999 |
Hoffmann, Jules A; Kafatos, Fotis C; Janeway, Charles A; Ezekowitz, Alan R B Phylogenetic perspectives in innate immunity Article de journal Science, 284 (5418), p. 1313–1318, 1999, ISSN: 0036-8075. Résumé | BibTeX | Étiquettes: Active, Animals, Culicidae, hoffmann, Humans, Immunity, Immunological, infection, Innate, Insect Vectors, M3i, Mammals, Models, Phagocytosis, Phylogeny, Proteins @article{hoffmann_phylogenetic_1999, title = {Phylogenetic perspectives in innate immunity}, author = {Jules A Hoffmann and Fotis C Kafatos and Charles A Janeway and Alan R B Ezekowitz}, issn = {0036-8075}, year = {1999}, date = {1999-05-01}, journal = {Science}, volume = {284}, number = {5418}, pages = {1313--1318}, abstract = {The concept of innate immunity refers to the first-line host defense that serves to limit infection in the early hours after exposure to microorganisms. Recent data have highlighted similarities between pathogen recognition, signaling pathways, and effector mechanisms of innate immunity in Drosophila and mammals, pointing to a common ancestry of these defenses. In addition to its role in the early phase of defense, innate immunity in mammals appears to play a key role in stimulating the subsequent, clonal response of adaptive immunity.}, keywords = {Active, Animals, Culicidae, hoffmann, Humans, Immunity, Immunological, infection, Innate, Insect Vectors, M3i, Mammals, Models, Phagocytosis, Phylogeny, Proteins}, pubstate = {published}, tppubtype = {article} } The concept of innate immunity refers to the first-line host defense that serves to limit infection in the early hours after exposure to microorganisms. Recent data have highlighted similarities between pathogen recognition, signaling pathways, and effector mechanisms of innate immunity in Drosophila and mammals, pointing to a common ancestry of these defenses. In addition to its role in the early phase of defense, innate immunity in mammals appears to play a key role in stimulating the subsequent, clonal response of adaptive immunity. |
1997 |
Hoffmann, Jules A Immune responsiveness in vector insects Article de journal Proc. Natl. Acad. Sci. U.S.A., 94 (21), p. 11152–11153, 1997, ISSN: 0027-8424. BibTeX | Étiquettes: Animals, Anopheles, bacteria, Blood Proteins, Defensins, hoffmann, Humans, Insect Vectors, Life Cycle Stages, M3i, Malaria, Mammals, Plasmodium @article{hoffmann_immune_1997, title = {Immune responsiveness in vector insects}, author = {Jules A Hoffmann}, issn = {0027-8424}, year = {1997}, date = {1997-10-01}, journal = {Proc. Natl. Acad. Sci. U.S.A.}, volume = {94}, number = {21}, pages = {11152--11153}, keywords = {Animals, Anopheles, bacteria, Blood Proteins, Defensins, hoffmann, Humans, Insect Vectors, Life Cycle Stages, M3i, Malaria, Mammals, Plasmodium}, pubstate = {published}, tppubtype = {article} } |
1990 |
Lagueux, Marie; Lwoff, L; Meister, Marie; Goltzené, F; Hoffmann, Jules A cDNAs from neurosecretory cells of brains of Locusta migratoria (Insecta, Orthoptera) encoding a novel member of the superfamily of insulins Article de journal Eur. J. Biochem., 187 (1), p. 249–254, 1990, ISSN: 0014-2956. Résumé | BibTeX | Étiquettes: Animals, Base Sequence, DNA, Genes, Grasshoppers, hoffmann, Humans, Insulin, M3i, Multigene Family, Nervous System, Neuropeptides, Neurosecretory Systems, Nucleic Acid, Nucleic Acid Hybridization, Oligonucleotide Probes, RNA, Sequence Homology @article{lagueux_cdnas_1990, title = {cDNAs from neurosecretory cells of brains of Locusta migratoria (Insecta, Orthoptera) encoding a novel member of the superfamily of insulins}, author = {Marie Lagueux and L Lwoff and Marie Meister and F Goltzené and Jules A Hoffmann}, issn = {0014-2956}, year = {1990}, date = {1990-01-01}, journal = {Eur. J. Biochem.}, volume = {187}, number = {1}, pages = {249--254}, abstract = {From neurohaemal lobes of corpora cardiaca of Locusta migratoria a 5-kDa peptide has been isolated and its sequence established [see the accompanying paper, by Hietter et al. (1990) Eur. J. Biochem. 187, 241-247]. We have designed oligonucleotide probes from the peptide sequence of this molecule and screened a library prepared from mRNA of the neurosecretory cell region of the brain of this insect. Several positive cDNAs were isolated, the combined nucleotide sequences of which predict a large precursor of 145 residues (15770 Da) containing the newly isolated 5-kDa peptide. The peptide is flanked by regions homologous to the A and B chains of the superfamily of insulins. The overall organization of the precursor is as follows: signal peptide/domain homologous to the B chain of insulins/C (connecting)-peptide (corresponding to the newly isolated 5-kDa peptide)/domain homologous to the A chain of insulins. The numbers and relative positions of the cysteines of the Locusta peptide are equivalent to those of the other members of the insulin superfamily and most of the hydrophobic core residues are conserved.}, keywords = {Animals, Base Sequence, DNA, Genes, Grasshoppers, hoffmann, Humans, Insulin, M3i, Multigene Family, Nervous System, Neuropeptides, Neurosecretory Systems, Nucleic Acid, Nucleic Acid Hybridization, Oligonucleotide Probes, RNA, Sequence Homology}, pubstate = {published}, tppubtype = {article} } From neurohaemal lobes of corpora cardiaca of Locusta migratoria a 5-kDa peptide has been isolated and its sequence established [see the accompanying paper, by Hietter et al. (1990) Eur. J. Biochem. 187, 241-247]. We have designed oligonucleotide probes from the peptide sequence of this molecule and screened a library prepared from mRNA of the neurosecretory cell region of the brain of this insect. Several positive cDNAs were isolated, the combined nucleotide sequences of which predict a large precursor of 145 residues (15770 Da) containing the newly isolated 5-kDa peptide. The peptide is flanked by regions homologous to the A and B chains of the superfamily of insulins. The overall organization of the precursor is as follows: signal peptide/domain homologous to the B chain of insulins/C (connecting)-peptide (corresponding to the newly isolated 5-kDa peptide)/domain homologous to the A chain of insulins. The numbers and relative positions of the cysteines of the Locusta peptide are equivalent to those of the other members of the insulin superfamily and most of the hydrophobic core residues are conserved. |