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2018 |
Goto, Akira; Okado, Kiyoshi; Martins, Nelson; Cai, Hua; Barbier, Vincent; Lamiable, Olivier; Troxler, Laurent; Santiago, Estelle; Kuhn, Lauriane; Paik, Donggi; Silverman, Neal; Holleufer, Andreas; Hartmann, Rune; Liu, Jiyong; Peng, Tao; Hoffmann, Jules A; Meignin, Carine; Daeffler, Laurent; Imler, Jean-Luc The Kinase IKKβ Regulates a STING- and NF-κB-Dependent Antiviral Response Pathway in Drosophila Article de journal Immunity, (49), p. 225-234, 2018. Résumé | Liens | BibTeX | Étiquettes: antiviral immunity, C19orf12, Dicistrovirus, hoffmann, IKKβ, IMD pathway, imler, innate immunity, M3i, meignin, NF-κB, picornavirus, STING @article{Goto2018, title = {The Kinase IKKβ Regulates a STING- and NF-κB-Dependent Antiviral Response Pathway in Drosophila}, author = {Akira Goto and Kiyoshi Okado and Nelson Martins and Hua Cai and Vincent Barbier and Olivier Lamiable and Laurent Troxler and Estelle Santiago and Lauriane Kuhn and Donggi Paik and Neal Silverman and Andreas Holleufer and Rune Hartmann and Jiyong Liu and Tao Peng and Jules A Hoffmann and Carine Meignin and Laurent Daeffler and Jean-Luc Imler}, editor = {Elsevier Inc.}, url = {https://doi.org/10.1016/j.immuni.2018.07.013}, doi = {j.immuni.2018.07.013}, year = {2018}, date = {2018-08-21}, journal = {Immunity}, number = {49}, pages = {225-234}, abstract = {Antiviral immunity in Drosophila involves RNA interference and poorly characterized inducible responses. Here, we showed that two components of the IMD pathway, the kinase dIKKβ and the transcription factor Relish, were required to control infection by two picorna-like viruses. We identified a set of genes induced by viral infection and regulated by dIKKβ and Relish, which included an ortholog of STING. We showed that dSTING participated in the control of infection by picorna-like viruses, acting upstream of dIKKβ to regulate expression of Nazo, an antiviral factor. Our data reveal an antiviral function for STING in an animal model devoid of interferons and suggest an evolutionarily ancient role for this molecule in antiviral immunity.}, keywords = {antiviral immunity, C19orf12, Dicistrovirus, hoffmann, IKKβ, IMD pathway, imler, innate immunity, M3i, meignin, NF-κB, picornavirus, STING}, pubstate = {published}, tppubtype = {article} } Antiviral immunity in Drosophila involves RNA interference and poorly characterized inducible responses. Here, we showed that two components of the IMD pathway, the kinase dIKKβ and the transcription factor Relish, were required to control infection by two picorna-like viruses. We identified a set of genes induced by viral infection and regulated by dIKKβ and Relish, which included an ortholog of STING. We showed that dSTING participated in the control of infection by picorna-like viruses, acting upstream of dIKKβ to regulate expression of Nazo, an antiviral factor. Our data reveal an antiviral function for STING in an animal model devoid of interferons and suggest an evolutionarily ancient role for this molecule in antiviral immunity. |
Ferreira, Flávia Viana; Aguiar, Eric Roberto Guimarães Rocha; Olmo, Roenick Proveti; de Oliveira, Karla Pollyanna Vieira; Silva, Emanuele Guimarães; Sant'Anna, Maurício Roberto Viana; de Gontijo, Nelder Figueiredo; Kroon, Erna Geessien; Imler, Jean-Luc; Marques, João Trindade The small non-coding RNA response to virus infection in the Leishmania vector Lutzomyia longipalpis Article de journal PLoS Negl Trop Dis, 12 (6), p. e0006569, 2018, ISSN: 1935-2735. Résumé | Liens | BibTeX | Étiquettes: Animals, Host-Pathogen Interactions, imler, Insect Vectors, Leishmania, M3i, ncRNA, Psychodidae, RNA, RNA Interference, Small Interfering, Untranslated, Vesicular stomatitis Indiana virus, Viral @article{ferreira_small_2018, title = {The small non-coding RNA response to virus infection in the Leishmania vector Lutzomyia longipalpis}, author = {Flávia Viana Ferreira and Eric Roberto Guimarães Rocha Aguiar and Roenick Proveti Olmo and Karla Pollyanna Vieira de Oliveira and Emanuele Guimarães Silva and Maurício Roberto Viana Sant'Anna and Nelder Figueiredo de Gontijo and Erna Geessien Kroon and Jean-Luc Imler and João Trindade Marques}, doi = {10.1371/journal.pntd.0006569}, issn = {1935-2735}, year = {2018}, date = {2018-01-01}, journal = {PLoS Negl Trop Dis}, volume = {12}, number = {6}, pages = {e0006569}, abstract = {Sandflies are well known vectors for Leishmania but also transmit a number of arthropod-borne viruses (arboviruses). Few studies have addressed the interaction between sandflies and arboviruses. RNA interference (RNAi) mechanisms utilize small non-coding RNAs to regulate different aspects of host-pathogen interactions. The small interfering RNA (siRNA) pathway is a broad antiviral mechanism in insects. In addition, at least in mosquitoes, another RNAi mechanism mediated by PIWI interacting RNAs (piRNAs) is activated by viral infection. Finally, endogenous microRNAs (miRNA) may also regulate host immune responses. Here, we analyzed the small non-coding RNA response to Vesicular stomatitis virus (VSV) infection in the sandfly Lutzoymia longipalpis. We detected abundant production of virus-derived siRNAs after VSV infection in adult sandflies. However, there was no production of virus-derived piRNAs and only mild changes in the expression of vector miRNAs in response to infection. We also observed abundant production of virus-derived siRNAs against two other viruses in Lutzomyia Lulo cells. Together, our results suggest that the siRNA but not the piRNA pathway mediates an antiviral response in sandflies. In agreement with this hypothesis, pre-treatment of cells with dsRNA against VSV was able to inhibit viral replication while knock-down of the central siRNA component, Argonaute-2, led to increased virus levels. Our work begins to elucidate the role of RNAi mechanisms in the interaction between L. longipalpis and viruses and should also open the way for studies with other sandfly-borne pathogens.}, keywords = {Animals, Host-Pathogen Interactions, imler, Insect Vectors, Leishmania, M3i, ncRNA, Psychodidae, RNA, RNA Interference, Small Interfering, Untranslated, Vesicular stomatitis Indiana virus, Viral}, pubstate = {published}, tppubtype = {article} } Sandflies are well known vectors for Leishmania but also transmit a number of arthropod-borne viruses (arboviruses). Few studies have addressed the interaction between sandflies and arboviruses. RNA interference (RNAi) mechanisms utilize small non-coding RNAs to regulate different aspects of host-pathogen interactions. The small interfering RNA (siRNA) pathway is a broad antiviral mechanism in insects. In addition, at least in mosquitoes, another RNAi mechanism mediated by PIWI interacting RNAs (piRNAs) is activated by viral infection. Finally, endogenous microRNAs (miRNA) may also regulate host immune responses. Here, we analyzed the small non-coding RNA response to Vesicular stomatitis virus (VSV) infection in the sandfly Lutzoymia longipalpis. We detected abundant production of virus-derived siRNAs after VSV infection in adult sandflies. However, there was no production of virus-derived piRNAs and only mild changes in the expression of vector miRNAs in response to infection. We also observed abundant production of virus-derived siRNAs against two other viruses in Lutzomyia Lulo cells. Together, our results suggest that the siRNA but not the piRNA pathway mediates an antiviral response in sandflies. In agreement with this hypothesis, pre-treatment of cells with dsRNA against VSV was able to inhibit viral replication while knock-down of the central siRNA component, Argonaute-2, led to increased virus levels. Our work begins to elucidate the role of RNAi mechanisms in the interaction between L. longipalpis and viruses and should also open the way for studies with other sandfly-borne pathogens. |
2017 |
Kuhn, Lauriane; Majzoub, Karim; Einhorn, Evelyne; Chicher, Johana; Pompon, Julien; Imler, Jean-Luc; Hammann, Philippe; Meignin, Carine Definition of a RACK1 Interaction Network in Drosophila melanogaster Using SWATH-MS Article de journal G3 (Bethesda), 2017, ISSN: 2160-1836. Résumé | Liens | BibTeX | Étiquettes: Drosophila melaogaster, imler, M3i, Mass Spectrometry, meignin, RACK1, Ribosome, Translation @article{kuhn_definition_2017, title = {Definition of a RACK1 Interaction Network in Drosophila melanogaster Using SWATH-MS}, author = {Lauriane Kuhn and Karim Majzoub and Evelyne Einhorn and Johana Chicher and Julien Pompon and Jean-Luc Imler and Philippe Hammann and Carine Meignin}, doi = {10.1534/g3.117.042564}, issn = {2160-1836}, year = {2017}, date = {2017-12-31}, journal = {G3 (Bethesda)}, abstract = {Receptor for Activated C kinase 1 (RACK1) is a scaffold protein that has been found in association with several signaling complexes, and with the 40S subunit of the ribosome. Using the model organism Drosophila melanogaster, we recently showed that RACK1 is required at the ribosome for IRES-mediated translation of viruses. Here, we report a proteomic characterization of the interactome of RACK1 in Drosophila S2 cells. We carried out Label-Free quantitation using both Data-Dependent and Data-Independent Acquisition and observed a significant advantage for the Sequential Window Acquisition of all THeoretical fragment-ion spectra (SWATH) method both in terms of identification of interactants and quantification of low abundance proteins. These data represent the first SWATH spectral library available for Drosophila and will be a useful resource for the community. A total of 52 interacting proteins were identified, including several molecules involved in translation such as structural components of the ribosome, factors regulating translation initiation or elongation and RNA binding proteins. Among these 52 proteins, 15 were identified as partners by the SWATH strategy only. Interestingly, these 15 proteins are significantly enriched for the functions translation and nucleic acid binding. This enrichment reflects the engagement of RACK1 at the ribosome and highlights the added value of SWATH analysis. A functional screen did not reveal any protein sharing the interesting properties of RACK1, which is required for IRES-dependent translation and not essential for cell viability. Intriguingly however, 10 of the RACK1 partners identified restrict replication of Cricket paralysis virus, an IRES-containing virus.}, keywords = {Drosophila melaogaster, imler, M3i, Mass Spectrometry, meignin, RACK1, Ribosome, Translation}, pubstate = {published}, tppubtype = {article} } Receptor for Activated C kinase 1 (RACK1) is a scaffold protein that has been found in association with several signaling complexes, and with the 40S subunit of the ribosome. Using the model organism Drosophila melanogaster, we recently showed that RACK1 is required at the ribosome for IRES-mediated translation of viruses. Here, we report a proteomic characterization of the interactome of RACK1 in Drosophila S2 cells. We carried out Label-Free quantitation using both Data-Dependent and Data-Independent Acquisition and observed a significant advantage for the Sequential Window Acquisition of all THeoretical fragment-ion spectra (SWATH) method both in terms of identification of interactants and quantification of low abundance proteins. These data represent the first SWATH spectral library available for Drosophila and will be a useful resource for the community. A total of 52 interacting proteins were identified, including several molecules involved in translation such as structural components of the ribosome, factors regulating translation initiation or elongation and RNA binding proteins. Among these 52 proteins, 15 were identified as partners by the SWATH strategy only. Interestingly, these 15 proteins are significantly enriched for the functions translation and nucleic acid binding. This enrichment reflects the engagement of RACK1 at the ribosome and highlights the added value of SWATH analysis. A functional screen did not reveal any protein sharing the interesting properties of RACK1, which is required for IRES-dependent translation and not essential for cell viability. Intriguingly however, 10 of the RACK1 partners identified restrict replication of Cricket paralysis virus, an IRES-containing virus. |
Mussabekova, Assel; Daeffler, Laurent; Imler, Jean-Luc Innate and intrinsic antiviral immunity in Drosophila Article de journal Cell. Mol. Life Sci., 2017, ISSN: 1420-9071. Résumé | Liens | BibTeX | Étiquettes: Argonaute 2, Dicer-2, IMD pathway, imler, Jak/STAT pathway, M3i, NF-κB @article{mussabekova_innate_2017, title = {Innate and intrinsic antiviral immunity in Drosophila}, author = {Assel Mussabekova and Laurent Daeffler and Jean-Luc Imler}, doi = {10.1007/s00018-017-2453-9}, issn = {1420-9071}, year = {2017}, date = {2017-01-01}, journal = {Cell. Mol. Life Sci.}, abstract = {The fruit fly Drosophila melanogaster has been a valuable model to investigate the genetic mechanisms of innate immunity. Initially focused on the resistance to bacteria and fungi, these studies have been extended to include antiviral immunity over the last decade. Like all living organisms, insects are continually exposed to viruses and have developed efficient defense mechanisms. We review here our current understanding on antiviral host defense in fruit flies. A major antiviral defense in Drosophila is RNA interference, in particular the small interfering (si) RNA pathway. In addition, complex inducible responses and restriction factors contribute to the control of infections. Some of the genes involved in these pathways have been conserved through evolution, highlighting loci that may account for susceptibility to viral infections in humans. Other genes are not conserved and represent species-specific innovations.}, keywords = {Argonaute 2, Dicer-2, IMD pathway, imler, Jak/STAT pathway, M3i, NF-κB}, pubstate = {published}, tppubtype = {article} } The fruit fly Drosophila melanogaster has been a valuable model to investigate the genetic mechanisms of innate immunity. Initially focused on the resistance to bacteria and fungi, these studies have been extended to include antiviral immunity over the last decade. Like all living organisms, insects are continually exposed to viruses and have developed efficient defense mechanisms. We review here our current understanding on antiviral host defense in fruit flies. A major antiviral defense in Drosophila is RNA interference, in particular the small interfering (si) RNA pathway. In addition, complex inducible responses and restriction factors contribute to the control of infections. Some of the genes involved in these pathways have been conserved through evolution, highlighting loci that may account for susceptibility to viral infections in humans. Other genes are not conserved and represent species-specific innovations. |
2016 |
Paro, Simona; Imler, Jean-Luc Encyclopedia of Immunobiology Book Chapter Ratcliffe, M (Ed.): 1 , Chapitre “Immunity in insects”, p. 454-461, Elsevier, 2016. BibTeX | Étiquettes: imler, Immunity, Insect, M3i @inbook{Paro0000, title = {Encyclopedia of Immunobiology}, author = {Simona Paro and Jean-Luc Imler}, editor = {M Ratcliffe}, year = {2016}, date = {2016-08-01}, volume = {1}, pages = {454-461}, publisher = {Elsevier}, chapter = {“Immunity in insects”}, keywords = {imler, Immunity, Insect, M3i}, pubstate = {published}, tppubtype = {inbook} } |
Lamiable, Olivier; Kellenberger, Christine; Kemp, Cordula; Troxler, Laurent; Pelte, Nadège; Boutros, Michael; Marques, Joao Trindade; Daeffler, Laurent; Hoffmann, Jules A; Roussel, Alain; Imler, Jean-Luc Cytokine Diedel and a viral homologue suppress the IMD pathway in Drosophila Article de journal PNAS, 113 (3), p. 698–703, 2016, ISSN: 0027-8424, 1091-6490. Résumé | Liens | BibTeX | Étiquettes: antiviral immunity, bioinformatic, cytokine, Edin, hoffmann, imler, M3i, Sindbis Virus, virokine @article{lamiable_cytokine_2016, title = {Cytokine Diedel and a viral homologue suppress the IMD pathway in Drosophila}, author = {Olivier Lamiable and Christine Kellenberger and Cordula Kemp and Laurent Troxler and Nadège Pelte and Michael Boutros and Joao Trindade Marques and Laurent Daeffler and Jules A Hoffmann and Alain Roussel and Jean-Luc Imler}, url = {http://www.pnas.org/content/113/3/698.abstract}, doi = {10.1073/pnas.1516122113}, issn = {0027-8424, 1091-6490}, year = {2016}, date = {2016-01-19}, urldate = {2016-01-07}, journal = {PNAS}, volume = {113}, number = {3}, pages = {698–703}, abstract = {Viruses are obligatory intracellular parasites that suffer strong evolutionary pressure from the host immune system. Rapidly evolving viral genomes can adapt to this pressure by acquiring genes that counteract host defense mechanisms. For example, many vertebrate DNA viruses have hijacked cellular genes encoding cytokines or cytokine receptors to disrupt host cell communication. Insect viruses express suppressors of RNA interference or apoptosis, highlighting the importance of these cell intrinsic antiviral mechanisms in invertebrates. Here, we report the identification and characterization of a family of proteins encoded by insect DNA viruses that are homologous to a 12-kDa circulating protein encoded by the virus-induced Drosophila gene diedel (die). We show that die mutant flies have shortened lifespan and succumb more rapidly than controls when infected with Sindbis virus. This reduced viability is associated with deregulated activation of the immune deficiency (IMD) pathway of host defense and can be rescued by mutations in the genes encoding the homolog of IKKγ or IMD itself. Our results reveal an endogenous pathway that is exploited by insect viruses to modulate NF-κB signaling and promote fly survival during the antiviral response.}, keywords = {antiviral immunity, bioinformatic, cytokine, Edin, hoffmann, imler, M3i, Sindbis Virus, virokine}, pubstate = {published}, tppubtype = {article} } Viruses are obligatory intracellular parasites that suffer strong evolutionary pressure from the host immune system. Rapidly evolving viral genomes can adapt to this pressure by acquiring genes that counteract host defense mechanisms. For example, many vertebrate DNA viruses have hijacked cellular genes encoding cytokines or cytokine receptors to disrupt host cell communication. Insect viruses express suppressors of RNA interference or apoptosis, highlighting the importance of these cell intrinsic antiviral mechanisms in invertebrates. Here, we report the identification and characterization of a family of proteins encoded by insect DNA viruses that are homologous to a 12-kDa circulating protein encoded by the virus-induced Drosophila gene diedel (die). We show that die mutant flies have shortened lifespan and succumb more rapidly than controls when infected with Sindbis virus. This reduced viability is associated with deregulated activation of the immune deficiency (IMD) pathway of host defense and can be rescued by mutations in the genes encoding the homolog of IKKγ or IMD itself. Our results reveal an endogenous pathway that is exploited by insect viruses to modulate NF-κB signaling and promote fly survival during the antiviral response. |
Lamiable, Olivier; Arnold, Johan; da de Faria, Isaque Joao Silva; Olmo, Roenick Proveti; Bergami, Francesco; Meignin, Carine; Hoffmann, Jules A; Marques, Joao Trindade; Imler, Jean-Luc Analysis of the Contribution of Hemocytes and Autophagy to Drosophila Antiviral Immunity Article de journal J. Virol., 90 (11), p. 5415–5426, 2016, ISSN: 0022-538X, 1098-5514. Liens | BibTeX | Étiquettes: antiviral immunity, Autophagy, Hemocytes, hoffmann, imler, M3i, meignin @article{lamiable_analysis_2016, title = {Analysis of the Contribution of Hemocytes and Autophagy to Drosophila Antiviral Immunity}, author = {Olivier Lamiable and Johan Arnold and Isaque Joao Silva da de Faria and Roenick Proveti Olmo and Francesco Bergami and Carine Meignin and Jules A Hoffmann and Joao Trindade Marques and Jean-Luc Imler}, url = {http://jvi.asm.org/content/90/11/5415}, doi = {10.1128/JVI.00238-16}, issn = {0022-538X, 1098-5514}, year = {2016}, date = {2016-01-01}, urldate = {2016-06-05}, journal = {J. Virol.}, volume = {90}, number = {11}, pages = {5415--5426}, keywords = {antiviral immunity, Autophagy, Hemocytes, hoffmann, imler, M3i, meignin}, pubstate = {published}, tppubtype = {article} } |
Marques, João T; Imler, Jean-Luc The diversity of insect antiviral immunity: insights from viruses Article de journal Current Opinion in Microbiology, 32 , p. 71–76, 2016, ISSN: 1369-5274. Résumé | Liens | BibTeX | Étiquettes: imler, M3i @article{marques_diversity_2016, title = {The diversity of insect antiviral immunity: insights from viruses}, author = {João T Marques and Jean-Luc Imler}, url = {http://www.sciencedirect.com/science/article/pii/S1369527416300571}, doi = {10.1016/j.mib.2016.05.002}, issn = {1369-5274}, year = {2016}, date = {2016-01-01}, urldate = {2016-06-05}, journal = {Current Opinion in Microbiology}, volume = {32}, pages = {71--76}, abstract = {Insects represent over 70% of all animal species. Recent virome analyses reveal unprecedented genetic diversity of insect viruses, which appears to match that of their hosts. Thus, insect-virus interactions may provide information on a vast repertoire of antiviral immune mechanisms. Tapping into this diversity is challenging because of several constraints imposed by the uniqueness of each insect model. Nevertheless, it is clear that many conserved and divergent pathways participate in the control of viral infection in insects. Co-evolution between hosts and viruses favors the development of immune evasion mechanisms by the pathogen. Viral suppressors can offer unique perspective on host pathways and emphasize the importance of RNA interference, apoptosis, but also NF-κB pathways and translation control in insect antiviral immunity.}, keywords = {imler, M3i}, pubstate = {published}, tppubtype = {article} } Insects represent over 70% of all animal species. Recent virome analyses reveal unprecedented genetic diversity of insect viruses, which appears to match that of their hosts. Thus, insect-virus interactions may provide information on a vast repertoire of antiviral immune mechanisms. Tapping into this diversity is challenging because of several constraints imposed by the uniqueness of each insect model. Nevertheless, it is clear that many conserved and divergent pathways participate in the control of viral infection in insects. Co-evolution between hosts and viruses favors the development of immune evasion mechanisms by the pathogen. Viral suppressors can offer unique perspective on host pathways and emphasize the importance of RNA interference, apoptosis, but also NF-κB pathways and translation control in insect antiviral immunity. |
Martins, Nelson; Imler, Jean-Luc; Meignin, Carine Discovery of novel targets for antivirals: learning from flies Article de journal Curr Opin Virol, 20 , p. 64–70, 2016, ISSN: 1879-6265. Résumé | Liens | BibTeX | Étiquettes: antiviral, imler, M3i, meignin, target @article{martins_discovery_2016, title = {Discovery of novel targets for antivirals: learning from flies}, author = {Nelson Martins and Jean-Luc Imler and Carine Meignin}, url = {http://www.sciencedirect.com/science/article/pii/S1879625716301274}, doi = {10.1016/j.coviro.2016.09.005}, issn = {1879-6265}, year = {2016}, date = {2016-01-01}, journal = {Curr Opin Virol}, volume = {20}, pages = {64--70}, abstract = {Developing antiviral drugs is challenging due to the small number of targets in viruses, and the rapid evolution of viral genes. Animals have evolved a number of efficient antiviral defence mechanisms, which can serve as a source of inspiration for novel therapies. The genetically tractable insect Drosophila belongs to the most diverse group of animals. Genetic and transcriptomic analyses have recently identified Drosophila genes encoding viral restriction factors. Some of them represent evolutionary novelties and their characterization may provide hints for the design of directly acting antivirals. In addition, functional screens revealed conserved host factors required for efficient viral translation, such as the ribosomal protein RACK1 and the release factor Pelo. These proteins are promising candidates for host-targeted antivirals.}, keywords = {antiviral, imler, M3i, meignin, target}, pubstate = {published}, tppubtype = {article} } Developing antiviral drugs is challenging due to the small number of targets in viruses, and the rapid evolution of viral genes. Animals have evolved a number of efficient antiviral defence mechanisms, which can serve as a source of inspiration for novel therapies. The genetically tractable insect Drosophila belongs to the most diverse group of animals. Genetic and transcriptomic analyses have recently identified Drosophila genes encoding viral restriction factors. Some of them represent evolutionary novelties and their characterization may provide hints for the design of directly acting antivirals. In addition, functional screens revealed conserved host factors required for efficient viral translation, such as the ribosomal protein RACK1 and the release factor Pelo. These proteins are promising candidates for host-targeted antivirals. |
Lamiable, Olivier; Meignin, Carine; Imler, Jean-Luc WntD and Diedel: Two immunomodulatory cytokines in Drosophila immunity Article de journal Fly (Austin), 10 (4), p. 187–194, 2016, ISSN: 1933-6942. Résumé | Liens | BibTeX | Étiquettes: Cytokines, Drosophila, IMD pathway, imler, innate immunity, M3i, meignin, virus @article{lamiable_wntd_2016, title = {WntD and Diedel: Two immunomodulatory cytokines in Drosophila immunity}, author = {Olivier Lamiable and Carine Meignin and Jean-Luc Imler}, url = {http://www.tandfonline.com/doi/abs/10.1080/19336934.2016.1202387?journalCode=kfly20}, doi = {10.1080/19336934.2016.1202387}, issn = {1933-6942}, year = {2016}, date = {2016-01-01}, journal = {Fly (Austin)}, volume = {10}, number = {4}, pages = {187--194}, abstract = {Remarkable progress has been made on the understanding of the basic mechanisms of innate immunity in flies, from sensing infection to production of effector molecules. However, how the immune response is orchestrated at the level of the organism remains poorly understood. While cytokines activating immune responses, such as Spaetzle or Unpaired-3, have been identified and characterized in Drosophila, much less is known regarding immunosuppressor cytokines. In a recent publication, we reported the identification of a novel cytokine, Diedel, which acts as systemic negative regulator of the IMD pathway. Here, we discuss the similarities between Diedel and WntD, another immunomodulatory cytokine and present evidence that the 2 molecules act independently from one another.}, keywords = {Cytokines, Drosophila, IMD pathway, imler, innate immunity, M3i, meignin, virus}, pubstate = {published}, tppubtype = {article} } Remarkable progress has been made on the understanding of the basic mechanisms of innate immunity in flies, from sensing infection to production of effector molecules. However, how the immune response is orchestrated at the level of the organism remains poorly understood. While cytokines activating immune responses, such as Spaetzle or Unpaired-3, have been identified and characterized in Drosophila, much less is known regarding immunosuppressor cytokines. In a recent publication, we reported the identification of a novel cytokine, Diedel, which acts as systemic negative regulator of the IMD pathway. Here, we discuss the similarities between Diedel and WntD, another immunomodulatory cytokine and present evidence that the 2 molecules act independently from one another. |
2015 |
Aguiar, Eric Roberto Guimarães Rocha; Olmo, Roenick Proveti; Paro, Simona; Ferreira, Flavia Viana; da de Faria, Isaque João Silva; Todjro, Yaovi Mathias Honore; Lobo, Francisco Pereira; Kroon, Erna Geessien; Meignin, Carine; Gatherer, Derek; Imler, Jean-Luc; Marques, João Trindade Sequence-independent characterization of viruses based on the pattern of viral small RNAs produced by the host Article de journal Nucleic Acids Research, 43 (13), p. 6191–6206, 2015, ISSN: 1362-4962. Résumé | Liens | BibTeX | Étiquettes: Animals, Contig Mapping, Female, imler, insects, M3i, meignin, Ovary, Plants, RNA, Sequence Analysis, Small Untranslated, Vertebrates, Viral, Viral Tropism, viruses @article{aguiar_sequence-independent_2015, title = {Sequence-independent characterization of viruses based on the pattern of viral small RNAs produced by the host}, author = {Eric Roberto Guimarães Rocha Aguiar and Roenick Proveti Olmo and Simona Paro and Flavia Viana Ferreira and Isaque João Silva da de Faria and Yaovi Mathias Honore Todjro and Francisco Pereira Lobo and Erna Geessien Kroon and Carine Meignin and Derek Gatherer and Jean-Luc Imler and João Trindade Marques}, url = {http://nar.oxfordjournals.org/lookup/doi/10.1093/nar/gkv587}, doi = {10.1093/nar/gkv587}, issn = {1362-4962}, year = {2015}, date = {2015-07-01}, journal = {Nucleic Acids Research}, volume = {43}, number = {13}, pages = {6191--6206}, abstract = {Virus surveillance in vector insects is potentially of great benefit to public health. Large-scale sequencing of small and long RNAs has previously been used to detect viruses, but without any formal comparison of different strategies. Furthermore, the identification of viral sequences largely depends on similarity searches against reference databases. Here, we developed a sequence-independent strategy based on virus-derived small RNAs produced by the host response, such as the RNA interference pathway. In insects, we compared sequences of small and long RNAs, demonstrating that viral sequences are enriched in the small RNA fraction. We also noted that the small RNA size profile is a unique signature for each virus and can be used to identify novel viral sequences without known relatives in reference databases. Using this strategy, we characterized six novel viruses in the viromes of laboratory fruit flies and wild populations of two insect vectors: mosquitoes and sandflies. We also show that the small RNA profile could be used to infer viral tropism for ovaries among other aspects of virus biology. Additionally, our results suggest that virus detection utilizing small RNAs can also be applied to vertebrates, although not as efficiently as to plants and insects.}, keywords = {Animals, Contig Mapping, Female, imler, insects, M3i, meignin, Ovary, Plants, RNA, Sequence Analysis, Small Untranslated, Vertebrates, Viral, Viral Tropism, viruses}, pubstate = {published}, tppubtype = {article} } Virus surveillance in vector insects is potentially of great benefit to public health. Large-scale sequencing of small and long RNAs has previously been used to detect viruses, but without any formal comparison of different strategies. Furthermore, the identification of viral sequences largely depends on similarity searches against reference databases. Here, we developed a sequence-independent strategy based on virus-derived small RNAs produced by the host response, such as the RNA interference pathway. In insects, we compared sequences of small and long RNAs, demonstrating that viral sequences are enriched in the small RNA fraction. We also noted that the small RNA size profile is a unique signature for each virus and can be used to identify novel viral sequences without known relatives in reference databases. Using this strategy, we characterized six novel viruses in the viromes of laboratory fruit flies and wild populations of two insect vectors: mosquitoes and sandflies. We also show that the small RNA profile could be used to infer viral tropism for ovaries among other aspects of virus biology. Additionally, our results suggest that virus detection utilizing small RNAs can also be applied to vertebrates, although not as efficiently as to plants and insects. |
Majzoub, Karim; Imler, Jean-Luc Encyclopedia of Molecular Cell Biology and Molecular Medicine Book Chapter Verlag, Wiley-VCH (Ed.): 1 , Chapitre « RNAi to treat virus infections », p. 192-228, GmbH & Co. KGaA, 2015. Résumé | Liens | BibTeX | Étiquettes: antiviral, Argonaute, Delivery, imler, Immunity, lipofection, M3i, microRNA (miRNA), RNA Virus Infections, RNAi, small hairpin RNA (shRNA), small interfering RNA (siRNA) @inbook{Majzoub2015, title = {Encyclopedia of Molecular Cell Biology and Molecular Medicine}, author = {Karim Majzoub and Jean-Luc Imler}, editor = {Wiley-VCH Verlag}, doi = {10.1002/3527600906.mcb.201500003}, year = {2015}, date = {2015-04-28}, volume = {1}, pages = {192-228}, publisher = {GmbH & Co. KGaA}, chapter = {« RNAi to treat virus infections »}, abstract = {In spite of its young age, the field of RNA interference has already yielded major advances in the laboratory. This sequence-specific mechanism of gene regulation also holds strong promise for the development of a new generation of drugs, in particular to control the everlasting threat of viral infections. Here, the mechanisms and pathways of RNA interference are reviewed, with emphasis placed on how RNA silencing forms a potent antiviral immune mechanism in plants and invertebrates. The approaches developed to use RNA interference to control viral infections in mammals are then described. Finally, the problems encountered while translating this revolutionary technology into the clinic are presented, and the advances currently developed to overcome these limitations are discussed.}, keywords = {antiviral, Argonaute, Delivery, imler, Immunity, lipofection, M3i, microRNA (miRNA), RNA Virus Infections, RNAi, small hairpin RNA (shRNA), small interfering RNA (siRNA)}, pubstate = {published}, tppubtype = {inbook} } In spite of its young age, the field of RNA interference has already yielded major advances in the laboratory. This sequence-specific mechanism of gene regulation also holds strong promise for the development of a new generation of drugs, in particular to control the everlasting threat of viral infections. Here, the mechanisms and pathways of RNA interference are reviewed, with emphasis placed on how RNA silencing forms a potent antiviral immune mechanism in plants and invertebrates. The approaches developed to use RNA interference to control viral infections in mammals are then described. Finally, the problems encountered while translating this revolutionary technology into the clinic are presented, and the advances currently developed to overcome these limitations are discussed. |
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 |
Chtarbanova, Stanislava; Lamiable, Olivier; Lee, Kwang-Zin; Galiana, Delphine; Troxler, Laurent; Meignin, Carine; Hetru, Charles; Hoffmann, Jules A; Daeffler, Laurent; Imler, Jean-Luc Drosophila C virus systemic infection leads to intestinal obstruction Article de journal Journal of Virology, 88 (24), p. 14057–14069, 2014, ISSN: 1098-5514. Résumé | Liens | BibTeX | Étiquettes: Animals, bioinformatic, Dicistroviridae, Female, Gastrointestinal Tract, Gene Expression Profiling, hoffmann, imler, Intestinal Obstruction, M3i, meignin, Muscle, Nodaviridae, Sindbis Virus, Smooth, Viral Tropism @article{chtarbanova_drosophila_2014, title = {Drosophila C virus systemic infection leads to intestinal obstruction}, author = {Stanislava Chtarbanova and Olivier Lamiable and Kwang-Zin Lee and Delphine Galiana and Laurent Troxler and Carine Meignin and Charles Hetru and Jules A Hoffmann and Laurent Daeffler and Jean-Luc Imler}, url = {http://jvi.asm.org/content/88/24/14057}, doi = {10.1128/JVI.02320-14}, issn = {1098-5514}, year = {2014}, date = {2014-12-01}, journal = {Journal of Virology}, volume = {88}, number = {24}, pages = {14057--14069}, abstract = {Drosophila C virus (DCV) is a positive-sense RNA virus belonging to the Dicistroviridae family. This natural pathogen of the model organism Drosophila melanogaster is commonly used to investigate antiviral host defense in flies, which involves both RNA interference and inducible responses. Although lethality is used routinely as a readout for the efficiency of the antiviral immune response in these studies, virus-induced pathologies in flies still are poorly understood. Here, we characterize the pathogenesis associated with systemic DCV infection. Comparison of the transcriptome of flies infected with DCV or two other positive-sense RNA viruses, Flock House virus and Sindbis virus, reveals that DCV infection, unlike those of the other two viruses, represses the expression of a large number of genes. Several of these genes are expressed specifically in the midgut and also are repressed by starvation. We show that systemic DCV infection triggers a nutritional stress in Drosophila which results from intestinal obstruction with the accumulation of peritrophic matrix at the entry of the midgut and the accumulation of the food ingested in the crop, a blind muscular food storage organ. The related virus cricket paralysis virus (CrPV), which efficiently grows in Drosophila, does not trigger this pathology. We show that DCV, but not CrPV, infects the smooth muscles surrounding the crop, causing extensive cytopathology and strongly reducing the rate of contractions. We conclude that the pathogenesis associated with systemic DCV infection results from the tropism of the virus for an important organ within the foregut of dipteran insects, the crop. IMPORTANCE: DCV is one of the few identified natural viral pathogens affecting the model organism Drosophila melanogaster. As such, it is an important virus for the deciphering of host-virus interactions in insects. We characterize here the pathogenesis associated with DCV infection in flies and show that it results from the tropism of the virus for an essential but poorly characterized organ in the digestive tract, the crop. Our results may have relevance for other members of the Dicistroviridae, some of which are pathogenic to beneficial or pest insect species.}, keywords = {Animals, bioinformatic, Dicistroviridae, Female, Gastrointestinal Tract, Gene Expression Profiling, hoffmann, imler, Intestinal Obstruction, M3i, meignin, Muscle, Nodaviridae, Sindbis Virus, Smooth, Viral Tropism}, pubstate = {published}, tppubtype = {article} } Drosophila C virus (DCV) is a positive-sense RNA virus belonging to the Dicistroviridae family. This natural pathogen of the model organism Drosophila melanogaster is commonly used to investigate antiviral host defense in flies, which involves both RNA interference and inducible responses. Although lethality is used routinely as a readout for the efficiency of the antiviral immune response in these studies, virus-induced pathologies in flies still are poorly understood. Here, we characterize the pathogenesis associated with systemic DCV infection. Comparison of the transcriptome of flies infected with DCV or two other positive-sense RNA viruses, Flock House virus and Sindbis virus, reveals that DCV infection, unlike those of the other two viruses, represses the expression of a large number of genes. Several of these genes are expressed specifically in the midgut and also are repressed by starvation. We show that systemic DCV infection triggers a nutritional stress in Drosophila which results from intestinal obstruction with the accumulation of peritrophic matrix at the entry of the midgut and the accumulation of the food ingested in the crop, a blind muscular food storage organ. The related virus cricket paralysis virus (CrPV), which efficiently grows in Drosophila, does not trigger this pathology. We show that DCV, but not CrPV, infects the smooth muscles surrounding the crop, causing extensive cytopathology and strongly reducing the rate of contractions. We conclude that the pathogenesis associated with systemic DCV infection results from the tropism of the virus for an important organ within the foregut of dipteran insects, the crop. IMPORTANCE: DCV is one of the few identified natural viral pathogens affecting the model organism Drosophila melanogaster. As such, it is an important virus for the deciphering of host-virus interactions in insects. We characterize here the pathogenesis associated with DCV infection in flies and show that it results from the tropism of the virus for an essential but poorly characterized organ in the digestive tract, the crop. Our results may have relevance for other members of the Dicistroviridae, some of which are pathogenic to beneficial or pest insect species. |
Lamiable, Olivier; Imler, Jean-Luc Induced antiviral innate immunity in Drosophila Article de journal Current Opinion in Microbiology, 20 , p. 62–68, 2014, ISSN: 1879-0364. Résumé | Liens | BibTeX | Étiquettes: Animals, Gene Expression Regulation, Host-Pathogen Interactions, imler, Immunity, Innate, M3i, RNA Viruses, Signal Transduction @article{lamiable_induced_2014, title = {Induced antiviral innate immunity in Drosophila}, author = {Olivier Lamiable and Jean-Luc Imler}, doi = {10.1016/j.mib.2014.05.006}, issn = {1879-0364}, year = {2014}, date = {2014-08-01}, journal = {Current Opinion in Microbiology}, volume = {20}, pages = {62--68}, abstract = {Immunity to viral infections in the model organism Drosophila melanogaster involves both RNA interference and additional induced responses. The latter include not only cellular mechanisms such as programmed cell death and autophagy, but also the induction of a large set of genes, some of which contribute to the control of viral replication and resistance to infection. This induced response to infection is complex and involves both virus-specific and cell-type specific mechanisms. We review here recent developments, from the sensing of viral infection to the induction of signaling pathways and production of antiviral effector molecules. Our current understanding, although still partial, validates the Drosophila model of antiviral induced immunity for insect pests and disease vectors, as well as for mammals.}, keywords = {Animals, Gene Expression Regulation, Host-Pathogen Interactions, imler, Immunity, Innate, M3i, RNA Viruses, Signal Transduction}, pubstate = {published}, tppubtype = {article} } Immunity to viral infections in the model organism Drosophila melanogaster involves both RNA interference and additional induced responses. The latter include not only cellular mechanisms such as programmed cell death and autophagy, but also the induction of a large set of genes, some of which contribute to the control of viral replication and resistance to infection. This induced response to infection is complex and involves both virus-specific and cell-type specific mechanisms. We review here recent developments, from the sensing of viral infection to the induction of signaling pathways and production of antiviral effector molecules. Our current understanding, although still partial, validates the Drosophila model of antiviral induced immunity for insect pests and disease vectors, as well as for mammals. |
Goto, Akira; Fukuyama, Hidehiro; Imler, Jean-Luc; Hoffmann, Jules A The chromatin regulator DMAP1 modulates activity of the nuclear factor B (NF-B) transcription factor Relish in the Drosophila innate immune response Article de journal The Journal of Biological Chemistry, 289 (30), p. 20470–20476, 2014, ISSN: 1083-351X. Résumé | Liens | BibTeX | Étiquettes: Animals, Cell Line, Chromatin Assembly and Disassembly, Epistasis, Escherichia coli, Escherichia coli Infections, Genetic, hoffmann, imler, Immunity, Innate, M3i, NF-kappa B, Repressor Proteins, Signal Transduction, Transcription Factors @article{goto_chromatin_2014, title = {The chromatin regulator DMAP1 modulates activity of the nuclear factor B (NF-B) transcription factor Relish in the Drosophila innate immune response}, author = {Akira Goto and Hidehiro Fukuyama and Jean-Luc Imler and Jules A Hoffmann}, doi = {10.1074/jbc.C114.553719}, issn = {1083-351X}, year = {2014}, date = {2014-07-01}, journal = {The Journal of Biological Chemistry}, volume = {289}, number = {30}, pages = {20470--20476}, abstract = {The host defense of the model organism Drosophila is under the control of two major signaling cascades controlling transcription factors of the NF-B family, the Toll and the immune deficiency (IMD) pathways. The latter shares extensive similarities with the mammalian TNF-R pathway and was initially discovered for its role in anti-Gram-negative bacterial reactions. A previous interactome study from this laboratory reported that an unexpectedly large number of proteins are binding to the canonical components of the IMD pathway. Here, we focus on DNA methyltransferase-associated protein 1 (DMAP1), which this study identified as an interactant of Relish, a Drosophila transcription factor reminiscent of the mammalian p105 NF-B protein. We show that silencing of DMAP1 expression both in S2 cells and in flies results in a significant reduction of Escherichia coli-induced expression of antimicrobial peptides. Epistatic analysis indicates that DMAP1 acts in parallel or downstream of Relish. Co-immunoprecipitation experiments further reveal that, in addition to Relish, DMAP1 also interacts with Akirin and the Brahma-associated protein 55 kDa (BAP55). Taken together, these results reveal that DMAP1 is a novel nuclear modulator of the IMD pathway, possibly acting at the level of chromatin remodeling.}, keywords = {Animals, Cell Line, Chromatin Assembly and Disassembly, Epistasis, Escherichia coli, Escherichia coli Infections, Genetic, hoffmann, imler, Immunity, Innate, M3i, NF-kappa B, Repressor Proteins, Signal Transduction, Transcription Factors}, pubstate = {published}, tppubtype = {article} } The host defense of the model organism Drosophila is under the control of two major signaling cascades controlling transcription factors of the NF-B family, the Toll and the immune deficiency (IMD) pathways. The latter shares extensive similarities with the mammalian TNF-R pathway and was initially discovered for its role in anti-Gram-negative bacterial reactions. A previous interactome study from this laboratory reported that an unexpectedly large number of proteins are binding to the canonical components of the IMD pathway. Here, we focus on DNA methyltransferase-associated protein 1 (DMAP1), which this study identified as an interactant of Relish, a Drosophila transcription factor reminiscent of the mammalian p105 NF-B protein. We show that silencing of DMAP1 expression both in S2 cells and in flies results in a significant reduction of Escherichia coli-induced expression of antimicrobial peptides. Epistatic analysis indicates that DMAP1 acts in parallel or downstream of Relish. Co-immunoprecipitation experiments further reveal that, in addition to Relish, DMAP1 also interacts with Akirin and the Brahma-associated protein 55 kDa (BAP55). Taken together, these results reveal that DMAP1 is a novel nuclear modulator of the IMD pathway, possibly acting at the level of chromatin remodeling. |
Imler, Jean-Luc; Hoffmann, Jules A Le défi des maladies infectieuses Book Chapter collection et prévenir demain, Ph. Cramer Guérir (Ed.): Chapitre « L’immunité innée », p. 167-174, Editions DOCIS, 2014, ISBN: 978-2-85525-390-9. Résumé | BibTeX | Étiquettes: hoffmann, imler, innate immunity, M3i, maladies infectieuses @inbook{Imler2014, title = {Le défi des maladies infectieuses}, author = {Jean-Luc Imler and Jules A Hoffmann}, editor = {Ph. Cramer collection Guérir et prévenir demain}, isbn = {978-2-85525-390-9}, year = {2014}, date = {2014-06-01}, pages = {167-174}, publisher = {Editions DOCIS}, chapter = {« L’immunité innée »}, abstract = {La lèpre fait des ravages dès l’Antiquité, les épidémies de peste tuent au Moyen Âge et celles de choléra dévastent l’Inde. La tuberculose émerge véritablement au XIXème siècle, la grippe espagnole a fait vingt millions de morts en 1918 et de nouvelles maladies apparaissent : les infections hospitalières, les hépatites, le SIDA, les fièvres hémorragiques, la légionellose,… Toutes ces maladies ont un point commun, ce sont des maladies infectieuses qui sont pour la médecine un vrai défi, tant elles sont dévastatrices. L’innovation a eu et continue à avoir un rôle essentiel dans la caractérisation de ces maladies, la découverte de l’agent responsable, leur traitement et leur prévention. Ce livre, dont les auteurs font partie des plus éminents spécialistes français et européens des maladies infectieuses décrit, de façon abordable par tous, aussi bien les découvertes et les inventions essentielles à ce domaine que les avancées médicales.}, keywords = {hoffmann, imler, innate immunity, M3i, maladies infectieuses}, pubstate = {published}, tppubtype = {inbook} } La lèpre fait des ravages dès l’Antiquité, les épidémies de peste tuent au Moyen Âge et celles de choléra dévastent l’Inde. La tuberculose émerge véritablement au XIXème siècle, la grippe espagnole a fait vingt millions de morts en 1918 et de nouvelles maladies apparaissent : les infections hospitalières, les hépatites, le SIDA, les fièvres hémorragiques, la légionellose,… Toutes ces maladies ont un point commun, ce sont des maladies infectieuses qui sont pour la médecine un vrai défi, tant elles sont dévastatrices. L’innovation a eu et continue à avoir un rôle essentiel dans la caractérisation de ces maladies, la découverte de l’agent responsable, leur traitement et leur prévention. Ce livre, dont les auteurs font partie des plus éminents spécialistes français et européens des maladies infectieuses décrit, de façon abordable par tous, aussi bien les découvertes et les inventions essentielles à ce domaine que les avancées médicales. |
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 |
Petrillo, Jessica E; Venter, Arno P; Short, James R; Gopal, Radhika; Deddouche, Safia; Lamiable, Olivier; Imler, Jean-Luc; Schneemann, Anette Cytoplasmic granule formation and translational inhibition of nodaviral RNAs in the absence of the double-stranded RNA binding protein B2 Article de journal Journal of Virology, 87 (24), p. 13409–13421, 2013, ISSN: 1098-5514. Résumé | Liens | BibTeX | Étiquettes: Animals, Capsid Proteins, Cell Line, Cricetinae, Cytoplasmic Granules, Double-Stranded, imler, M3i, Nodaviridae, Protein Biosynthesis, RNA, RNA Virus Infections, RNA-Binding Proteins, Viral, Viral Proteins @article{petrillo_cytoplasmic_2013, title = {Cytoplasmic granule formation and translational inhibition of nodaviral RNAs in the absence of the double-stranded RNA binding protein B2}, author = {Jessica E Petrillo and Arno P Venter and James R Short and Radhika Gopal and Safia Deddouche and Olivier Lamiable and Jean-Luc Imler and Anette Schneemann}, doi = {10.1128/JVI.02362-13}, issn = {1098-5514}, year = {2013}, date = {2013-12-01}, journal = {Journal of Virology}, volume = {87}, number = {24}, pages = {13409--13421}, abstract = {Flock House virus (FHV) is a positive-sense RNA insect virus with a bipartite genome. RNA1 encodes the RNA-dependent RNA polymerase, and RNA2 encodes the capsid protein. A third protein, B2, is translated from a subgenomic RNA3 derived from the 3' end of RNA1. B2 is a double-stranded RNA (dsRNA) binding protein that inhibits RNA silencing, a major antiviral defense pathway in insects. FHV is conveniently propagated in Drosophila melanogaster cells but can also be grown in mammalian cells. It was previously reported that B2 is dispensable for FHV RNA replication in BHK21 cells; therefore, we chose this cell line to generate a viral mutant that lacked the ability to produce B2. Consistent with published results, we found that RNA replication was indeed vigorous but the yield of progeny virus was negligible. Closer inspection revealed that infected cells contained very small amounts of coat protein despite an abundance of RNA2. B2 mutants that had reduced affinity for dsRNA produced analogous results, suggesting that the dsRNA binding capacity of B2 somehow played a role in coat protein synthesis. Using fluorescence in situ hybridization of FHV RNAs, we discovered that RNA2 is recruited into large cytoplasmic granules in the absence of B2, whereas the distribution of RNA1 remains largely unaffected. We conclude that B2, by binding to double-stranded regions in progeny RNA2, prevents recruitment of RNA2 into cellular structures, where it is translationally silenced. This represents a novel function of B2 that further contributes to successful completion of the nodaviral life cycle.}, keywords = {Animals, Capsid Proteins, Cell Line, Cricetinae, Cytoplasmic Granules, Double-Stranded, imler, M3i, Nodaviridae, Protein Biosynthesis, RNA, RNA Virus Infections, RNA-Binding Proteins, Viral, Viral Proteins}, pubstate = {published}, tppubtype = {article} } Flock House virus (FHV) is a positive-sense RNA insect virus with a bipartite genome. RNA1 encodes the RNA-dependent RNA polymerase, and RNA2 encodes the capsid protein. A third protein, B2, is translated from a subgenomic RNA3 derived from the 3' end of RNA1. B2 is a double-stranded RNA (dsRNA) binding protein that inhibits RNA silencing, a major antiviral defense pathway in insects. FHV is conveniently propagated in Drosophila melanogaster cells but can also be grown in mammalian cells. It was previously reported that B2 is dispensable for FHV RNA replication in BHK21 cells; therefore, we chose this cell line to generate a viral mutant that lacked the ability to produce B2. Consistent with published results, we found that RNA replication was indeed vigorous but the yield of progeny virus was negligible. Closer inspection revealed that infected cells contained very small amounts of coat protein despite an abundance of RNA2. B2 mutants that had reduced affinity for dsRNA produced analogous results, suggesting that the dsRNA binding capacity of B2 somehow played a role in coat protein synthesis. Using fluorescence in situ hybridization of FHV RNAs, we discovered that RNA2 is recruited into large cytoplasmic granules in the absence of B2, whereas the distribution of RNA1 remains largely unaffected. We conclude that B2, by binding to double-stranded regions in progeny RNA2, prevents recruitment of RNA2 into cellular structures, where it is translationally silenced. This represents a novel function of B2 that further contributes to successful completion of the nodaviral life cycle. |
2012 |
Ezekowitz, Alan R B; Dimarcq, Jean-Luc; Kafatos, Fotis; Levashina, Elena A; Ferrandon, Dominique; Hetru, Charles; Imler, Jean-Luc; Reichhart, Jean-Marc Lawrence's book review unfair to Hoffmann Article de journal Curr. Biol., 22 (12), p. R482, 2012, ISSN: 1879-0445. Liens | BibTeX | Étiquettes: Book Reviews as Topic, Ethics, ferrandon, imler, M3i, Professional, reichhart @article{ezekowitz_lawrences_2012, title = {Lawrence's book review unfair to Hoffmann}, author = {Alan R B Ezekowitz and Jean-Luc Dimarcq and Fotis Kafatos and Elena A Levashina and Dominique Ferrandon and Charles Hetru and Jean-Luc Imler and Jean-Marc Reichhart}, doi = {10.1016/j.cub.2012.05.015}, issn = {1879-0445}, year = {2012}, date = {2012-06-01}, journal = {Curr. Biol.}, volume = {22}, number = {12}, pages = {R482}, keywords = {Book Reviews as Topic, Ethics, ferrandon, imler, M3i, Professional, reichhart}, pubstate = {published}, tppubtype = {article} } |
Imler, Jean-Luc; Hoffmann, Jules A Nucleic Acid Sensors and Antiviral Immunity Book Chapter eds Sambhara, Fujita & T P (Ed.): Chapitre 1 : Antiviral responses in invertebrates, p. 1-18, Landes Bioscience, 2012. BibTeX | Étiquettes: antiviral immunity, hoffmann, imler, Invertebrate, M3i @inbook{Imler2012, title = {Nucleic Acid Sensors and Antiviral Immunity}, author = {Jean-Luc Imler and Jules A Hoffmann}, editor = {eds T. Fujita & P. Sambhara}, year = {2012}, date = {2012-06-01}, pages = {1-18}, publisher = {Landes Bioscience}, chapter = {1 : Antiviral responses in invertebrates}, keywords = {antiviral immunity, hoffmann, imler, Invertebrate, M3i}, pubstate = {published}, tppubtype = {inbook} } |
Goto, Akira; Imler, Jean-Luc Toll signaling in flies and mammals: two sorts of MyD88 Article de journal Immunity, 36 (4), p. 555–557, 2012, ISSN: 1097-4180. Résumé | Liens | BibTeX | Étiquettes: imler, M3i @article{goto_toll_2012, title = {Toll signaling in flies and mammals: two sorts of MyD88}, author = {Akira Goto and Jean-Luc Imler}, doi = {10.1016/j.immuni.2012.04.001}, issn = {1097-4180}, year = {2012}, date = {2012-04-01}, journal = {Immunity}, volume = {36}, number = {4}, pages = {555--557}, abstract = {The mammalian MyD88 signaling molecule participates in Toll receptor signaling within the cytoplasm. In this issue of Immunity, Marek and Kagan (2012) report that Drosophila (d)MyD88 acts instead at the plasma membrane to sort the signaling adaptor Tube.}, keywords = {imler, M3i}, pubstate = {published}, tppubtype = {article} } The mammalian MyD88 signaling molecule participates in Toll receptor signaling within the cytoplasm. In this issue of Immunity, Marek and Kagan (2012) report that Drosophila (d)MyD88 acts instead at the plasma membrane to sort the signaling adaptor Tube. |
Coste, Franck; Kemp, Cordula; Bobezeau, Vanessa; Hetru, Charles; Kellenberger, Christine; Imler, Jean-Luc; Roussel, Alain Crystal structure of Diedel, a marker of the immune response of Drosophila melanogaster Article de journal PloS One, 7 (3), p. e33416, 2012, ISSN: 1932-6203. Résumé | Liens | BibTeX | Étiquettes: Animals, Aphids, Crystallography, imler, Janus Kinases, M3i, Protein Folding, Protein Structure, Signal Transduction, STAT Transcription Factors, Tertiary, Transcription Factors, X-Ray @article{coste_crystal_2012, title = {Crystal structure of Diedel, a marker of the immune response of Drosophila melanogaster}, author = {Franck Coste and Cordula Kemp and Vanessa Bobezeau and Charles Hetru and Christine Kellenberger and Jean-Luc Imler and Alain Roussel}, doi = {10.1371/journal.pone.0033416}, issn = {1932-6203}, year = {2012}, date = {2012-01-01}, journal = {PloS One}, volume = {7}, number = {3}, pages = {e33416}, abstract = {BACKGROUND: The Drosophila melanogaster gene CG11501 is up regulated after a septic injury and was proposed to act as a negative regulator of the JAK/STAT signaling pathway. Diedel, the CG11501 gene product, is a small protein of 115 residues with 10 cysteines. METHODOLOGY/PRINCIPAL FINDINGS: We have produced Diedel in Drosophila S2 cells as an extra cellular protein thanks to its own signal peptide and solved its crystal structure at 1.15 Å resolution by SIRAS using an iodo derivative. Diedel is composed of two sub domains SD1 and SD2. SD1 is made of an antiparallel β-sheet covered by an α-helix and displays a ferredoxin-like fold. SD2 reveals a new protein fold made of loops connected by four disulfide bridges. Further structural analysis identified conserved hydrophobic residues on the surface of Diedel that may constitute a potential binding site. The existence of two conformations, cis and trans, for the proline 52 may be of interest as prolyl peptidyl isomerisation has been shown to play a role in several physiological mechanisms. The genome of D. melanogaster contains two other genes coding for proteins homologous to Diedel, namely CG43228 and CG34329. Strikingly, apart from Drosophila and the pea aphid Acyrthosiphon pisum, Diedel-related sequences were exclusively identified in a few insect DNA viruses of the Baculoviridae and Ascoviridae families. CONCLUSION/SIGNIFICANCE: Diedel, a marker of the Drosophila antimicrobial/antiviral response, is a member of a small family of proteins present in drosophilids, aphids and DNA viruses infecting lepidopterans. Diedel is an extracellular protein composed of two sub-domains. Two special structural features (hydrophobic surface patch and cis/trans conformation for proline 52) may indicate a putative interaction site, and support an extra cellular signaling function for Diedel, which is in accordance with its proposed role as negative regulator of the JAK/STAT signaling pathway.}, keywords = {Animals, Aphids, Crystallography, imler, Janus Kinases, M3i, Protein Folding, Protein Structure, Signal Transduction, STAT Transcription Factors, Tertiary, Transcription Factors, X-Ray}, pubstate = {published}, tppubtype = {article} } BACKGROUND: The Drosophila melanogaster gene CG11501 is up regulated after a septic injury and was proposed to act as a negative regulator of the JAK/STAT signaling pathway. Diedel, the CG11501 gene product, is a small protein of 115 residues with 10 cysteines. METHODOLOGY/PRINCIPAL FINDINGS: We have produced Diedel in Drosophila S2 cells as an extra cellular protein thanks to its own signal peptide and solved its crystal structure at 1.15 Å resolution by SIRAS using an iodo derivative. Diedel is composed of two sub domains SD1 and SD2. SD1 is made of an antiparallel β-sheet covered by an α-helix and displays a ferredoxin-like fold. SD2 reveals a new protein fold made of loops connected by four disulfide bridges. Further structural analysis identified conserved hydrophobic residues on the surface of Diedel that may constitute a potential binding site. The existence of two conformations, cis and trans, for the proline 52 may be of interest as prolyl peptidyl isomerisation has been shown to play a role in several physiological mechanisms. The genome of D. melanogaster contains two other genes coding for proteins homologous to Diedel, namely CG43228 and CG34329. Strikingly, apart from Drosophila and the pea aphid Acyrthosiphon pisum, Diedel-related sequences were exclusively identified in a few insect DNA viruses of the Baculoviridae and Ascoviridae families. CONCLUSION/SIGNIFICANCE: Diedel, a marker of the Drosophila antimicrobial/antiviral response, is a member of a small family of proteins present in drosophilids, aphids and DNA viruses infecting lepidopterans. Diedel is an extracellular protein composed of two sub-domains. Two special structural features (hydrophobic surface patch and cis/trans conformation for proline 52) may indicate a putative interaction site, and support an extra cellular signaling function for Diedel, which is in accordance with its proposed role as negative regulator of the JAK/STAT signaling pathway. |
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} } |
Chtarbanova, Stanislava; Imler, Jean-Luc Immunité innée antivirale chez la drosophile Article de journal Virologie, 15 (5), p. 296-306, 2011, ISSN: 1267-8694. Résumé | Liens | BibTeX | Étiquettes: *RNA Interference, antiviral immunity, Argonaute, dicer, helicase, imler, M3i, viruses @article{Chtarbanova2011, title = {Immunité innée antivirale chez la drosophile}, author = {Stanislava Chtarbanova and Jean-Luc Imler}, url = {http://www.jle.com/fr/revues/vir/e-docs/immunite_innee_antivirale_chez_la_drosophile_290366/article.phtml?tab=texte}, doi = {10.1684/vir.2011.0417}, issn = {1267-8694}, year = {2011}, date = {2011-10-01}, journal = {Virologie}, volume = {15}, number = {5}, pages = {296-306}, abstract = {La drosophile est utilisée depuis une quinzaine d’années comme modèle pour l’étude des mécanismes de l’immunité innée contre les infections bactériennes et fongiques. Les mécanismes de défense de cet insecte contre les infections virales sont maintenant abordés. L’interférence ARN joue un rôle essentiel dans la détection et le contrôle des virus. Ce mécanisme implique la reconnaissance des ARN double brins viraux par Dicer-2 et leur coupure pour former des petits ARN interférants (ARNsi) de 21 nucléotides. Ces ARNsi sont ensuite chargés sur l’enzyme Argonaute-2, qui inhibera spécifiquement les ARN viraux contenant une séquence complémentaire. Une réponse immunitaire inductible contribue également au contrôle des infections virales chez la drosophile. Cette réponse implique les voies de signalisation Toll et IMD, d’une part, (régulant des facteurs de transcription de la famille NF-κB) et JAK/STAT, d’autre part. On ne sait encore que peu de choses sur la nature des molécules effectrices régulées par ces voies de signalisation et sur les récepteurs qui les activent. Même si de nombreux points d’interrogation demeurent, l’intérêt du modèle drosophile pour identifier des mécanismes de défense antivirale conservés au cours de l’évolution, et impliqués dans la transmission des arbovirus par les moustiques, est aujourd’hui bien établi.}, keywords = {*RNA Interference, antiviral immunity, Argonaute, dicer, helicase, imler, M3i, viruses}, pubstate = {published}, tppubtype = {article} } La drosophile est utilisée depuis une quinzaine d’années comme modèle pour l’étude des mécanismes de l’immunité innée contre les infections bactériennes et fongiques. Les mécanismes de défense de cet insecte contre les infections virales sont maintenant abordés. L’interférence ARN joue un rôle essentiel dans la détection et le contrôle des virus. Ce mécanisme implique la reconnaissance des ARN double brins viraux par Dicer-2 et leur coupure pour former des petits ARN interférants (ARNsi) de 21 nucléotides. Ces ARNsi sont ensuite chargés sur l’enzyme Argonaute-2, qui inhibera spécifiquement les ARN viraux contenant une séquence complémentaire. Une réponse immunitaire inductible contribue également au contrôle des infections virales chez la drosophile. Cette réponse implique les voies de signalisation Toll et IMD, d’une part, (régulant des facteurs de transcription de la famille NF-κB) et JAK/STAT, d’autre part. On ne sait encore que peu de choses sur la nature des molécules effectrices régulées par ces voies de signalisation et sur les récepteurs qui les activent. Même si de nombreux points d’interrogation demeurent, l’intérêt du modèle drosophile pour identifier des mécanismes de défense antivirale conservés au cours de l’évolution, et impliqués dans la transmission des arbovirus par les moustiques, est aujourd’hui bien établi. |
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. |
2009 |
Kemp, Cordula; Imler, Jean-Luc Antiviral immunity in drosophila Article de journal Current Opinion in Immunology, 21 (1), p. 3–9, 2009, ISSN: 1879-0372. Résumé | Liens | BibTeX | Étiquettes: Animals, Argonaute Proteins, Caspases, DEAD-box RNA Helicases, Evolution, Gene Expression Regulation, Host-Pathogen Interactions, imler, M3i, Membrane Proteins, Molecular, Nuclear Proteins, Ribonuclease III, RNA, RNA Helicases, RNA Interference, RNA Virus Infections, RNA Viruses, RNA-Induced Silencing Complex, Viral, Virulence @article{kemp_antiviral_2009, title = {Antiviral immunity in drosophila}, author = {Cordula Kemp and Jean-Luc Imler}, doi = {10.1016/j.coi.2009.01.007}, issn = {1879-0372}, year = {2009}, date = {2009-02-01}, journal = {Current Opinion in Immunology}, volume = {21}, number = {1}, pages = {3--9}, abstract = {Genetic analysis of the drosophila antiviral response indicates that RNA interference plays a major role. This contrasts with the situation in mammals, where interferon-induced responses mediate innate antiviral host-defense. An inducible response also contributes to antiviral immunity in drosophila, and similarities in the sensing and signaling of viral infection are becoming apparent between drosophila and mammals. In particular, DExD/H box helicases appear to play a crucial role in the cytosolic detection of viral RNAs in flies and mammals.}, keywords = {Animals, Argonaute Proteins, Caspases, DEAD-box RNA Helicases, Evolution, Gene Expression Regulation, Host-Pathogen Interactions, imler, M3i, Membrane Proteins, Molecular, Nuclear Proteins, Ribonuclease III, RNA, RNA Helicases, RNA Interference, RNA Virus Infections, RNA Viruses, RNA-Induced Silencing Complex, Viral, Virulence}, pubstate = {published}, tppubtype = {article} } Genetic analysis of the drosophila antiviral response indicates that RNA interference plays a major role. This contrasts with the situation in mammals, where interferon-induced responses mediate innate antiviral host-defense. An inducible response also contributes to antiviral immunity in drosophila, and similarities in the sensing and signaling of viral infection are becoming apparent between drosophila and mammals. In particular, DExD/H box helicases appear to play a crucial role in the cytosolic detection of viral RNAs in flies and mammals. |
Berry, Bassam; Deddouche, Safia; Kirschner, Doris; Imler, Jean-Luc; Antoniewski, Christophe Viral suppressors of RNA silencing hinder exogenous and endogenous small RNA pathways in Drosophila Article de journal PloS One, 4 (6), p. e5866, 2009, ISSN: 1932-6203. Résumé | Liens | BibTeX | Étiquettes: Animals, Antiviral Agents, Crosses, Double-Stranded, Gene Silencing, Genetic, Genetically Modified, Heterozygote, imler, Invertebrate, M3i, Photoreceptor Cells, Reverse Transcriptase Polymerase Chain Reaction, RNA, RNA Interference, Transgenes @article{berry_viral_2009, title = {Viral suppressors of RNA silencing hinder exogenous and endogenous small RNA pathways in Drosophila}, author = {Bassam Berry and Safia Deddouche and Doris Kirschner and Jean-Luc Imler and Christophe Antoniewski}, doi = {10.1371/journal.pone.0005866}, issn = {1932-6203}, year = {2009}, date = {2009-01-01}, journal = {PloS One}, volume = {4}, number = {6}, pages = {e5866}, abstract = {BACKGROUND: In plants and insects, RNA interference (RNAi) is the main responder against viruses and shapes the basis of antiviral immunity. Viruses counter this defense by expressing viral suppressors of RNAi (VSRs). While VSRs in Drosophila melanogaster were shown to inhibit RNAi through different modes of action, whether they act on other silencing pathways remained unexplored. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that expression of various plant and insect VSRs in transgenic flies does not perturb the Drosophila microRNA (miRNA) pathway; but in contrast, inhibits antiviral RNAi and the RNA silencing response triggered by inverted repeat transcripts, and injection of dsRNA or siRNA. Strikingly, these VSRs also suppressed transposon silencing by endogenous siRNAs (endo-siRNAs). CONCLUSIONS/SIGNIFICANCE: Our findings identify VSRs as tools to unravel small RNA pathways in insects and suggest a cosuppression of antiviral RNAi and endo-siRNA silencing by viruses during fly infections.}, keywords = {Animals, Antiviral Agents, Crosses, Double-Stranded, Gene Silencing, Genetic, Genetically Modified, Heterozygote, imler, Invertebrate, M3i, Photoreceptor Cells, Reverse Transcriptase Polymerase Chain Reaction, RNA, RNA Interference, Transgenes}, pubstate = {published}, tppubtype = {article} } BACKGROUND: In plants and insects, RNA interference (RNAi) is the main responder against viruses and shapes the basis of antiviral immunity. Viruses counter this defense by expressing viral suppressors of RNAi (VSRs). While VSRs in Drosophila melanogaster were shown to inhibit RNAi through different modes of action, whether they act on other silencing pathways remained unexplored. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that expression of various plant and insect VSRs in transgenic flies does not perturb the Drosophila microRNA (miRNA) pathway; but in contrast, inhibits antiviral RNAi and the RNA silencing response triggered by inverted repeat transcripts, and injection of dsRNA or siRNA. Strikingly, these VSRs also suppressed transposon silencing by endogenous siRNAs (endo-siRNAs). CONCLUSIONS/SIGNIFICANCE: Our findings identify VSRs as tools to unravel small RNA pathways in insects and suggest a cosuppression of antiviral RNAi and endo-siRNA silencing by viruses during fly infections. |
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. |
Huszar, Tünde; Imler, Jean-Luc Drosophila viruses and the study of antiviral host-defense Article de journal Advances in Virus Research, 72 , p. 227–265, 2008, ISSN: 0065-3527. Résumé | Liens | BibTeX | Étiquettes: Animals, Host-Pathogen Interactions, imler, Immunity, Innate, Insect Viruses, M3i, RNA Interference, RNA Viruses @article{huszar_drosophila_2008, title = {Drosophila viruses and the study of antiviral host-defense}, author = {Tünde Huszar and Jean-Luc Imler}, doi = {10.1016/S0065-3527(08)00406-5}, issn = {0065-3527}, year = {2008}, date = {2008-01-01}, journal = {Advances in Virus Research}, volume = {72}, pages = {227--265}, abstract = {The fruit fly Drosophila melanogaster is a powerful model to study host-pathogen interactions. Most studies so far have focused on extracellular pathogens such as bacteria and fungi. More recently, viruses have come to the front, and RNA interference was shown to play a critical role in the control of viral infections in drosophila. We review here our current knowledge on drosophila viruses. A diverse set of RNA viruses belonging to several families (Rhabdoviridae, Dicistroviridae, Birnaviridae, Reoviridae, Errantiviridae) has been reported in D. melanogaster. By contrast, no DNA virus has been recovered up to now. The drosophila viruses represent powerful tools to study virus-cell interactions in vivo. Analysis of the literature however reveals that for many of them, important gaps exist in our understanding of their replication cycle, genome organization, morphology or pathogenesis. The data obtained in the past few years on antiviral defense mechanisms in drosophila, which point to evolutionary conserved pathways, highlight the potential of the D. melanogaster model to study antiviral innate immunity and to better understand the complex interaction between arthropod-borne viruses and their insect vectors.}, keywords = {Animals, Host-Pathogen Interactions, imler, Immunity, Innate, Insect Viruses, M3i, RNA Interference, RNA Viruses}, pubstate = {published}, tppubtype = {article} } The fruit fly Drosophila melanogaster is a powerful model to study host-pathogen interactions. Most studies so far have focused on extracellular pathogens such as bacteria and fungi. More recently, viruses have come to the front, and RNA interference was shown to play a critical role in the control of viral infections in drosophila. We review here our current knowledge on drosophila viruses. A diverse set of RNA viruses belonging to several families (Rhabdoviridae, Dicistroviridae, Birnaviridae, Reoviridae, Errantiviridae) has been reported in D. melanogaster. By contrast, no DNA virus has been recovered up to now. The drosophila viruses represent powerful tools to study virus-cell interactions in vivo. Analysis of the literature however reveals that for many of them, important gaps exist in our understanding of their replication cycle, genome organization, morphology or pathogenesis. The data obtained in the past few years on antiviral defense mechanisms in drosophila, which point to evolutionary conserved pathways, highlight the potential of the D. melanogaster model to study antiviral innate immunity and to better understand the complex interaction between arthropod-borne viruses and their insect vectors. |
2007 |
Ferrandon, Dominique; Imler, Jean-Luc; Hetru, Charles; Hoffmann, Jules A The Drosophila systemic immune response: sensing and signalling during bacterial and fungal infections Article de journal Nat Rev Immunol, 7 , p. 862–74, 2007. Résumé | BibTeX | Étiquettes: Animals, Bacterial Infections/*immunology/microbiology, Drosophila melanogaster/genetics/*immunology/microbiology, ferrandon, hoffmann, imler, Immunity, M3i, Mycoses/*immunology/microbiology, Natural/genetics, Signal Transduction/genetics/*immunology @article{ferrandon_drosophila_2007b, title = {The Drosophila systemic immune response: sensing and signalling during bacterial and fungal infections}, author = {Dominique Ferrandon and Jean-Luc Imler and Charles Hetru and Jules A Hoffmann}, year = {2007}, date = {2007-11-01}, journal = {Nat Rev Immunol}, volume = {7}, pages = {862--74}, abstract = {A hallmark of the potent, multifaceted antimicrobial defence of Drosophila melanogaster is the challenge-induced synthesis of several families of antimicrobial peptides by cells in the fat body. The basic mechanisms of recognition of various types of microbial infections by the adult fly are now understood, often in great detail. We have further gained valuable insight into the infection-induced gene reprogramming by nuclear factor-kappaB (NF-kappaB) family members under the dependence of complex intracellular signalling cascades. The striking parallels between the adult fly response and mammalian innate immune defences described below point to a common ancestry and validate the relevance of the fly defence as a paradigm for innate immunity.}, keywords = {Animals, Bacterial Infections/*immunology/microbiology, Drosophila melanogaster/genetics/*immunology/microbiology, ferrandon, hoffmann, imler, Immunity, M3i, Mycoses/*immunology/microbiology, Natural/genetics, Signal Transduction/genetics/*immunology}, pubstate = {published}, tppubtype = {article} } A hallmark of the potent, multifaceted antimicrobial defence of Drosophila melanogaster is the challenge-induced synthesis of several families of antimicrobial peptides by cells in the fat body. The basic mechanisms of recognition of various types of microbial infections by the adult fly are now understood, often in great detail. We have further gained valuable insight into the infection-induced gene reprogramming by nuclear factor-kappaB (NF-kappaB) family members under the dependence of complex intracellular signalling cascades. The striking parallels between the adult fly response and mammalian innate immune defences described below point to a common ancestry and validate the relevance of the fly defence as a paradigm for innate immunity. |
Beutler, Bruce; Eidenschenk, Celine; Crozat, Karine; Imler, Jean-Luc; Takeuchi, Osamu; Hoffmann, Jules A; Akira, Shizuo Genetic analysis of resistance to viral infection Article de journal Nature Reviews. Immunology, 7 (10), p. 753–766, 2007, ISSN: 1474-1741. Résumé | Liens | BibTeX | Étiquettes: Animals, Antiviral Agents, Disease Susceptibility, Drug Resistance, Eukaryotic Cells, hoffmann, Humans, imler, Immunity, M3i, Mutation, Viral, Virus Diseases, viruses @article{beutler_genetic_2007, title = {Genetic analysis of resistance to viral infection}, author = {Bruce Beutler and Celine Eidenschenk and Karine Crozat and Jean-Luc Imler and Osamu Takeuchi and Jules A Hoffmann and Shizuo Akira}, doi = {10.1038/nri2174}, issn = {1474-1741}, year = {2007}, date = {2007-10-01}, journal = {Nature Reviews. Immunology}, volume = {7}, number = {10}, pages = {753--766}, abstract = {As machines that reprogramme eukaryotic cells to suit their own purposes, viruses present a difficult problem for multicellular hosts, and indeed, have become one of the central pre-occupations of the immune system. Unable to permanently outpace individual viruses in an evolutionary footrace, higher eukaryotes have evolved broadly active mechanisms with which to sense viruses and suppress their proliferation. These mechanisms have recently been elucidated by a combination of forward and reverse genetic methods. Some of these mechanisms are clearly ancient, whereas others are relatively new. All are remarkably adept at discriminating self from non-self, and allow the host to cope with what might seem an impossible predicament.}, keywords = {Animals, Antiviral Agents, Disease Susceptibility, Drug Resistance, Eukaryotic Cells, hoffmann, Humans, imler, Immunity, M3i, Mutation, Viral, Virus Diseases, viruses}, pubstate = {published}, tppubtype = {article} } As machines that reprogramme eukaryotic cells to suit their own purposes, viruses present a difficult problem for multicellular hosts, and indeed, have become one of the central pre-occupations of the immune system. Unable to permanently outpace individual viruses in an evolutionary footrace, higher eukaryotes have evolved broadly active mechanisms with which to sense viruses and suppress their proliferation. These mechanisms have recently been elucidated by a combination of forward and reverse genetic methods. Some of these mechanisms are clearly ancient, whereas others are relatively new. All are remarkably adept at discriminating self from non-self, and allow the host to cope with what might seem an impossible predicament. |
Müller, Stefanie; Imler, Jean-Luc Dicing with viruses: microRNAs as antiviral factors Article de journal Immunity, 27 (1), p. 1–3, 2007, ISSN: 1074-7613. Résumé | Liens | BibTeX | Étiquettes: Animals, DEAD-box RNA Helicases, Endoribonucleases, imler, M3i, MicroRNAs, Ribonuclease III, RNA Interference, RNA Virus Infections @article{muller_dicing_2007, title = {Dicing with viruses: microRNAs as antiviral factors}, author = {Stefanie Müller and Jean-Luc Imler}, doi = {10.1016/j.immuni.2007.07.003}, issn = {1074-7613}, year = {2007}, date = {2007-07-01}, journal = {Immunity}, volume = {27}, number = {1}, pages = {1--3}, abstract = {In plants and invertebrates, Dicer genes play a critical role against infections by RNA viruses. In this issue, Otsuka et al. (2007) report that Dicer mutant mice are hypersusceptible to infection by the RNA virus VSV.}, keywords = {Animals, DEAD-box RNA Helicases, Endoribonucleases, imler, M3i, MicroRNAs, Ribonuclease III, RNA Interference, RNA Virus Infections}, pubstate = {published}, tppubtype = {article} } In plants and invertebrates, Dicer genes play a critical role against infections by RNA viruses. In this issue, Otsuka et al. (2007) report that Dicer mutant mice are hypersusceptible to infection by the RNA virus VSV. |
Weber, Alexander N R; Gangloff, Monique; Moncrieffe, Martin C; Hyvert, Yann; Imler, Jean-Luc; Gay, Nicholas J Role of the Spatzle Pro-domain in the generation of an active toll receptor ligand Article de journal The Journal of Biological Chemistry, 282 (18), p. 13522–13531, 2007, ISSN: 0021-9258. Résumé | Liens | BibTeX | Étiquettes: Animals, Cytokines, dimerization, imler, ligands, M3i, Post-Translational, Protein Binding, Protein Processing, Protein Structure, Signal Transduction, Tertiary, Toll-Like Receptors @article{weber_role_2007, title = {Role of the Spatzle Pro-domain in the generation of an active toll receptor ligand}, author = {Alexander N R Weber and Monique Gangloff and Martin C Moncrieffe and Yann Hyvert and Jean-Luc Imler and Nicholas J Gay}, doi = {10.1074/jbc.M700068200}, issn = {0021-9258}, year = {2007}, date = {2007-05-01}, journal = {The Journal of Biological Chemistry}, volume = {282}, number = {18}, pages = {13522--13531}, abstract = {The cytokine Spätzle is the ligand for Drosophila Toll, the prototype of an important family of membrane receptors that function in embryonic patterning and innate immunity. A dimeric precursor of Spätzle is processed by an endoprotease to produce a form (C-106) that cross-links Toll receptor ectodomains and establishes signaling. Here we show that before processing the pro-domain of Spätzle is required for correct biosynthesis and secretion. We mapped two loss-of-function mutations of Spätzle to a discrete site in the pro-domain and showed that the phenotype arises because of a defect in biosynthesis rather than signaling. We also report that the pro-domain and C-106 remain associated after cleavage and that this processed complex signals with the same characteristics as the C-terminal fragment. These results suggest that before activation the determinants on C-106 that bind specifically to Toll are sequestered by the pro-domain and that proteolytic processing causes conformational rearrangements that expose these determinants and enables binding to Toll. Furthermore, we show that the pro-domain is released when the Toll extracellular domain binds to the complex, a finding that has implications for the generation of a signaling-competent Toll dimer.}, keywords = {Animals, Cytokines, dimerization, imler, ligands, M3i, Post-Translational, Protein Binding, Protein Processing, Protein Structure, Signal Transduction, Tertiary, Toll-Like Receptors}, pubstate = {published}, tppubtype = {article} } The cytokine Spätzle is the ligand for Drosophila Toll, the prototype of an important family of membrane receptors that function in embryonic patterning and innate immunity. A dimeric precursor of Spätzle is processed by an endoprotease to produce a form (C-106) that cross-links Toll receptor ectodomains and establishes signaling. Here we show that before processing the pro-domain of Spätzle is required for correct biosynthesis and secretion. We mapped two loss-of-function mutations of Spätzle to a discrete site in the pro-domain and showed that the phenotype arises because of a defect in biosynthesis rather than signaling. We also report that the pro-domain and C-106 remain associated after cleavage and that this processed complex signals with the same characteristics as the C-terminal fragment. These results suggest that before activation the determinants on C-106 that bind specifically to Toll are sequestered by the pro-domain and that proteolytic processing causes conformational rearrangements that expose these determinants and enables binding to Toll. Furthermore, we show that the pro-domain is released when the Toll extracellular domain binds to the complex, a finding that has implications for the generation of a signaling-competent Toll dimer. |
Croker, Ben; Crozat, Karine; Berger, Michael; Xia, Yu; Sovath, Sosathya; Schaffer, Lana; Eleftherianos, Ioannis; Imler, Jean-Luc; Beutler, Bruce ATP-sensitive potassium channels mediate survival during infection in mammals and insects Article de journal Nature Genetics, 39 (12), p. 1453–1460, 2007, ISSN: 1546-1718. Résumé | Liens | BibTeX | Étiquettes: Animals, ATP-Binding Cassette Transporters, Cloning, Coronary Vessels, Crosses, Ethylnitrosourea, Genetic, Homozygote, imler, infection, Inwardly Rectifying, KATP Channels, Lipopolysaccharides, M3i, Mice, Molecular, Mutagenesis, Potassium Channels, Sulfonylurea Receptors @article{croker_atp-sensitive_2007, title = {ATP-sensitive potassium channels mediate survival during infection in mammals and insects}, author = {Ben Croker and Karine Crozat and Michael Berger and Yu Xia and Sosathya Sovath and Lana Schaffer and Ioannis Eleftherianos and Jean-Luc Imler and Bruce Beutler}, doi = {10.1038/ng.2007.25}, issn = {1546-1718}, year = {2007}, date = {2007-01-01}, journal = {Nature Genetics}, volume = {39}, number = {12}, pages = {1453--1460}, abstract = {Specific homeostatic mechanisms confer stability in innate immune responses, preventing injury or death from infection. Here we identify, from a screen of N-ethyl-N-nitrosourea-mutagenized mice, a mutation causing both profound susceptibility to infection by mouse cytomegalovirus and approximately 20,000-fold sensitization to lipopolysaccharide (LPS), poly(I.C) and immunostimulatory (CpG) DNA. The LPS hypersensitivity phenotype is not suppressed by mutations in Myd88, Trif, Tnf, Tnfrsf1a, Ifnb, Ifng or Stat1, genes contributing to LPS responses, and results from an abnormality extrinsic to hematopoietic cells. The phenotype is due to a null allele of Kcnj8, encoding Kir6.1, a protein that combines with SUR2 to form an ATP-sensitive potassium channel (K(ATP)) expressed in coronary artery smooth muscle and endothelial cells. In Drosophila melanogaster, suppression of dSUR by RNA interference similarly causes hypersensitivity to infection by flock house virus. Thus, K(ATP) evolved to serve a homeostatic function during infection, and in mammals it prevents coronary artery vasoconstriction induced by cytokines dependent on TLR and/or MDA5 immunoreceptors.}, keywords = {Animals, ATP-Binding Cassette Transporters, Cloning, Coronary Vessels, Crosses, Ethylnitrosourea, Genetic, Homozygote, imler, infection, Inwardly Rectifying, KATP Channels, Lipopolysaccharides, M3i, Mice, Molecular, Mutagenesis, Potassium Channels, Sulfonylurea Receptors}, pubstate = {published}, tppubtype = {article} } Specific homeostatic mechanisms confer stability in innate immune responses, preventing injury or death from infection. Here we identify, from a screen of N-ethyl-N-nitrosourea-mutagenized mice, a mutation causing both profound susceptibility to infection by mouse cytomegalovirus and approximately 20,000-fold sensitization to lipopolysaccharide (LPS), poly(I.C) and immunostimulatory (CpG) DNA. The LPS hypersensitivity phenotype is not suppressed by mutations in Myd88, Trif, Tnf, Tnfrsf1a, Ifnb, Ifng or Stat1, genes contributing to LPS responses, and results from an abnormality extrinsic to hematopoietic cells. The phenotype is due to a null allele of Kcnj8, encoding Kir6.1, a protein that combines with SUR2 to form an ATP-sensitive potassium channel (K(ATP)) expressed in coronary artery smooth muscle and endothelial cells. In Drosophila melanogaster, suppression of dSUR by RNA interference similarly causes hypersensitivity to infection by flock house virus. Thus, K(ATP) evolved to serve a homeostatic function during infection, and in mammals it prevents coronary artery vasoconstriction induced by cytokines dependent on TLR and/or MDA5 immunoreceptors. |
Galiana-Arnoux, Delphine; Deddouche, Safia; Imler, Jean-Luc Immunité antivirale chez la drosophile Article de journal Journal de la Société de Biologie, 201 (4), p. 359–365, 2007, ISSN: 1295-0661. Liens | BibTeX | Étiquettes: imler, M3i @article{galiana-arnoux_immunite_2007, title = {Immunité antivirale chez la drosophile}, author = {Delphine Galiana-Arnoux and Safia Deddouche and Jean-Luc Imler}, url = {http://www.biologie-journal.org/10.1051/jbio:2007906}, doi = {10.1051/jbio:2007906}, issn = {1295-0661}, year = {2007}, date = {2007-01-01}, urldate = {2015-11-26}, journal = {Journal de la Société de Biologie}, volume = {201}, number = {4}, pages = {359--365}, keywords = {imler, M3i}, pubstate = {published}, tppubtype = {article} } |
Galiana-Arnoux, Delphine; Deddouche, Safia; Imler, Jean-Luc [Antiviral immunity in drosophila] Article de journal Journal De La Société De Biologie, 201 (4), p. 359–365, 2007, ISSN: 1295-0661. Résumé | Liens | BibTeX | Étiquettes: imler, M3i @article{galiana-arnoux_[antiviral_2007, title = {[Antiviral immunity in drosophila]}, author = {Delphine Galiana-Arnoux and Safia Deddouche and Jean-Luc Imler}, doi = {10.1051/jbio:2007906}, issn = {1295-0661}, year = {2007}, date = {2007-01-01}, journal = {Journal De La Société De Biologie}, volume = {201}, number = {4}, pages = {359--365}, abstract = {Viral diseases represent a constant threat and an important cause of mortality worldwide. We have developed a model to study the response to RNA virus infection in the fruit-fly drosophila. This insect is a good model to study the genetic bases of innate immunity, which constitutes the first level of host-defense in animals. We have shown that viral infection in drosophila triggers a response different from that to bacterial or fungal infections. Our data at this stage point to the existence of at least two types of antiviral defense mechanisms. On one hand, viral infection triggers a JAK-STAT dependent transcriptional response that leads to the expression of antiviral molecules that remain to be characterized. On the other hand, viral RNAs are recognized by Dicer-2 and degraded in siRNAs, thus inducing RNA interference and degradation of viral RNAs. Strikingly, the drosophila antiviral response evokes by some aspects the interferon response in mammals (JAK-STAT pathway) and antiviral defenses in plants (RNA interference).}, keywords = {imler, M3i}, pubstate = {published}, tppubtype = {article} } Viral diseases represent a constant threat and an important cause of mortality worldwide. We have developed a model to study the response to RNA virus infection in the fruit-fly drosophila. This insect is a good model to study the genetic bases of innate immunity, which constitutes the first level of host-defense in animals. We have shown that viral infection in drosophila triggers a response different from that to bacterial or fungal infections. Our data at this stage point to the existence of at least two types of antiviral defense mechanisms. On one hand, viral infection triggers a JAK-STAT dependent transcriptional response that leads to the expression of antiviral molecules that remain to be characterized. On the other hand, viral RNAs are recognized by Dicer-2 and degraded in siRNAs, thus inducing RNA interference and degradation of viral RNAs. Strikingly, the drosophila antiviral response evokes by some aspects the interferon response in mammals (JAK-STAT pathway) and antiviral defenses in plants (RNA interference). |
2006 |
Evans, J D; Aronstein, K; Chen, Y P; Hetru, Charles; Imler, Jean-Luc; Jiang, H; Kanost, M; Thompson, G J; Zou, Z; Hultmark, D Immune pathways and defence mechanisms in honey bees Apis mellifera Article de journal Insect Molecular Biology, 15 (5), p. 645–656, 2006, ISSN: 0962-1075. Résumé | Liens | BibTeX | Étiquettes: Animals, Bees, Carrier Proteins, Genome, imler, Immunity, Insect, Janus Kinases, M3i, Multigene Family, Serine Endopeptidases, Signal Transduction, STAT Transcription Factors, Toll-Like Receptors @article{evans_immune_2006, title = {Immune pathways and defence mechanisms in honey bees Apis mellifera}, author = {J D Evans and K Aronstein and Y P Chen and Charles Hetru and Jean-Luc Imler and H Jiang and M Kanost and G J Thompson and Z Zou and D Hultmark}, doi = {10.1111/j.1365-2583.2006.00682.x}, issn = {0962-1075}, year = {2006}, date = {2006-10-01}, journal = {Insect Molecular Biology}, volume = {15}, number = {5}, pages = {645--656}, abstract = {Social insects are able to mount both group-level and individual defences against pathogens. Here we focus on individual defences, by presenting a genome-wide analysis of immunity in a social insect, the honey bee Apis mellifera. We present honey bee models for each of four signalling pathways associated with immunity, identifying plausible orthologues for nearly all predicted pathway members. When compared to the sequenced Drosophila and Anopheles genomes, honey bees possess roughly one-third as many genes in 17 gene families implicated in insect immunity. We suggest that an implied reduction in immune flexibility in bees reflects either the strength of social barriers to disease, or a tendency for bees to be attacked by a limited set of highly coevolved pathogens.}, keywords = {Animals, Bees, Carrier Proteins, Genome, imler, Immunity, Insect, Janus Kinases, M3i, Multigene Family, Serine Endopeptidases, Signal Transduction, STAT Transcription Factors, Toll-Like Receptors}, pubstate = {published}, tppubtype = {article} } Social insects are able to mount both group-level and individual defences against pathogens. Here we focus on individual defences, by presenting a genome-wide analysis of immunity in a social insect, the honey bee Apis mellifera. We present honey bee models for each of four signalling pathways associated with immunity, identifying plausible orthologues for nearly all predicted pathway members. When compared to the sequenced Drosophila and Anopheles genomes, honey bees possess roughly one-third as many genes in 17 gene families implicated in insect immunity. We suggest that an implied reduction in immune flexibility in bees reflects either the strength of social barriers to disease, or a tendency for bees to be attacked by a limited set of highly coevolved pathogens. |
Galiana-Arnoux, Delphine; Dostert, Catherine; Schneemann, Anette; Hoffmann, Jules A; Imler, Jean-Luc Essential function in vivo for Dicer-2 in host defense against RNA viruses in drosophila Article de journal Nature Immunology, 7 (6), p. 590–597, 2006, ISSN: 1529-2908. Résumé | Liens | BibTeX | Étiquettes: Animals, Genetically Modified, hoffmann, imler, M3i, Mutation, Nodaviridae, Ribonuclease III, RNA, RNA Helicases, RNA Interference, RNA Viruses, Viral, Viral Proteins, Virus Replication @article{galiana-arnoux_essential_2006, title = {Essential function in vivo for Dicer-2 in host defense against RNA viruses in drosophila}, author = {Delphine Galiana-Arnoux and Catherine Dostert and Anette Schneemann and Jules A Hoffmann and Jean-Luc Imler}, doi = {10.1038/ni1335}, issn = {1529-2908}, year = {2006}, date = {2006-06-01}, journal = {Nature Immunology}, volume = {7}, number = {6}, pages = {590--597}, abstract = {The fruit fly Drosophila melanogaster is a model system for studying innate immunity, including antiviral host defense. Infection with drosophila C virus triggers a transcriptional response that is dependent in part on the Jak kinase Hopscotch. Here we show that successful infection and killing of drosophila with the insect nodavirus flock house virus was strictly dependent on expression of the viral protein B2, a potent inhibitor of processing of double-stranded RNA mediated by the essential RNA interference factor Dicer. Conversely, flies with a loss-of-function mutation in the gene encoding Dicer-2 (Dcr-2) showed enhanced susceptibility to infection by flock house virus, drosophila C virus and Sindbis virus, members of three different families of RNA viruses. These data demonstrate the importance of RNA interference for controlling virus replication in vivo and establish Dcr-2 as a host susceptibility locus for virus infections.}, keywords = {Animals, Genetically Modified, hoffmann, imler, M3i, Mutation, Nodaviridae, Ribonuclease III, RNA, RNA Helicases, RNA Interference, RNA Viruses, Viral, Viral Proteins, Virus Replication}, pubstate = {published}, tppubtype = {article} } The fruit fly Drosophila melanogaster is a model system for studying innate immunity, including antiviral host defense. Infection with drosophila C virus triggers a transcriptional response that is dependent in part on the Jak kinase Hopscotch. Here we show that successful infection and killing of drosophila with the insect nodavirus flock house virus was strictly dependent on expression of the viral protein B2, a potent inhibitor of processing of double-stranded RNA mediated by the essential RNA interference factor Dicer. Conversely, flies with a loss-of-function mutation in the gene encoding Dicer-2 (Dcr-2) showed enhanced susceptibility to infection by flock house virus, drosophila C virus and Sindbis virus, members of three different families of RNA viruses. These data demonstrate the importance of RNA interference for controlling virus replication in vivo and establish Dcr-2 as a host susceptibility locus for virus infections. |
Chen, Li-Ying; Wang, Juinn-Chin; Hyvert, Yann; Lin, Hui-Ping; Perrimon, Norbert; Imler, Jean-Luc; Hsu, Jui-Chou Weckle is a zinc finger adaptor of the toll pathway in dorsoventral patterning of the Drosophila embryo Article de journal Current biology: CB, 16 (12), p. 1183–1193, 2006, ISSN: 0960-9822. Résumé | Liens | BibTeX | Étiquettes: Adaptor Proteins, Animals, Antigens, Biological, Body Patterning, Cell Membrane, Differentiation, dimerization, DNA-Binding Proteins, Embryo, Epistasis, Genetic, imler, Immunity, Immunologic, Innate, M3i, Models, Mutation, Nonmammalian, Phenotype, Phosphoproteins, Receptors, Signal Transducing, Toll-Like Receptors, Transcription Factors, Zinc Fingers @article{chen_weckle_2006, title = {Weckle is a zinc finger adaptor of the toll pathway in dorsoventral patterning of the Drosophila embryo}, author = {Li-Ying Chen and Juinn-Chin Wang and Yann Hyvert and Hui-Ping Lin and Norbert Perrimon and Jean-Luc Imler and Jui-Chou Hsu}, doi = {10.1016/j.cub.2006.05.050}, issn = {0960-9822}, year = {2006}, date = {2006-06-01}, journal = {Current biology: CB}, volume = {16}, number = {12}, pages = {1183--1193}, abstract = {BACKGROUND: The Drosophila Toll pathway takes part in both establishment of the embryonic dorsoventral axis and induction of the innate immune response in adults. Upon activation by the cytokine Spätzle, Toll interacts with the adaptor proteins DmMyD88 and Tube and the kinase Pelle and triggers degradation of the inhibitor Cactus, thus allowing the nuclear translocation of the transcription factor Dorsal/Dif. weckle (wek) was previously identified as a new dorsal group gene that encodes a putative zinc finger transcription factor. However, its role in the Toll pathway was unknown. RESULTS: Here, we isolated new wek alleles and demonstrated that cactus is epistatic to wek, which in turn is epistatic to Toll. Consistent with this, Wek localizes to the plasma membrane of embryos, independently of Toll signaling. Wek homodimerizes and associates with Toll. Moreover, Wek binds to and localizes DmMyD88 to the plasma membrane. Thus, Wek acts as an adaptor to assemble/stabilize a Toll/Wek/DmMyD88/Tube complex. Remarkably, unlike the DmMyD88/tube/pelle/cactus gene cassette of the Toll pathway, wek plays a minimal role, if any, in the immune defense against Gram-positive bacteria and fungi. CONCLUSIONS: We conclude that Wek is an adaptor to link Toll and DmMyD88 and is required for efficient recruitment of DmMyD88 to Toll. Unexpectedly, wek is dispensable for innate immune response, thus revealing differences in the Toll-mediated activation of Dorsal in the embryo and Dif in the fat body of adult flies.}, keywords = {Adaptor Proteins, Animals, Antigens, Biological, Body Patterning, Cell Membrane, Differentiation, dimerization, DNA-Binding Proteins, Embryo, Epistasis, Genetic, imler, Immunity, Immunologic, Innate, M3i, Models, Mutation, Nonmammalian, Phenotype, Phosphoproteins, Receptors, Signal Transducing, Toll-Like Receptors, Transcription Factors, Zinc Fingers}, pubstate = {published}, tppubtype = {article} } BACKGROUND: The Drosophila Toll pathway takes part in both establishment of the embryonic dorsoventral axis and induction of the innate immune response in adults. Upon activation by the cytokine Spätzle, Toll interacts with the adaptor proteins DmMyD88 and Tube and the kinase Pelle and triggers degradation of the inhibitor Cactus, thus allowing the nuclear translocation of the transcription factor Dorsal/Dif. weckle (wek) was previously identified as a new dorsal group gene that encodes a putative zinc finger transcription factor. However, its role in the Toll pathway was unknown. RESULTS: Here, we isolated new wek alleles and demonstrated that cactus is epistatic to wek, which in turn is epistatic to Toll. Consistent with this, Wek localizes to the plasma membrane of embryos, independently of Toll signaling. Wek homodimerizes and associates with Toll. Moreover, Wek binds to and localizes DmMyD88 to the plasma membrane. Thus, Wek acts as an adaptor to assemble/stabilize a Toll/Wek/DmMyD88/Tube complex. Remarkably, unlike the DmMyD88/tube/pelle/cactus gene cassette of the Toll pathway, wek plays a minimal role, if any, in the immune defense against Gram-positive bacteria and fungi. CONCLUSIONS: We conclude that Wek is an adaptor to link Toll and DmMyD88 and is required for efficient recruitment of DmMyD88 to Toll. Unexpectedly, wek is dispensable for innate immune response, thus revealing differences in the Toll-mediated activation of Dorsal in the embryo and Dif in the fat body of adult flies. |
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 |
Dostert, Catherine; Jouanguy, Emmanuelle; Irving, Phil; Troxler, Laurent; Galiana-Arnoux, Delphine; Hetru, Charles; Hoffmann, Jules A; Imler, Jean-Luc The Jak-STAT signaling pathway is required but not sufficient for the antiviral response of drosophila Article de journal Nature Immunology, 6 (9), p. 946–953, 2005, ISSN: 1529-2908. Résumé | Liens | BibTeX | Étiquettes: Animals, bioinformatic, DNA-Binding Proteins, Genetic, Genetically Modified, hoffmann, imler, Insect Viruses, Janus Kinase 1, M3i, Male, Oligonucleotide Array Sequence Analysis, Promoter Regions, Protein-Tyrosine Kinases, Signal Transduction, STAT1 Transcription Factor, Trans-Activators @article{dostert_jak-stat_2005, title = {The Jak-STAT signaling pathway is required but not sufficient for the antiviral response of drosophila}, author = {Catherine Dostert and Emmanuelle Jouanguy and Phil Irving and Laurent Troxler and Delphine Galiana-Arnoux and Charles Hetru and Jules A Hoffmann and Jean-Luc Imler}, doi = {10.1038/ni1237}, issn = {1529-2908}, year = {2005}, date = {2005-01-01}, journal = {Nature Immunology}, volume = {6}, number = {9}, pages = {946--953}, abstract = {The response of drosophila to bacterial and fungal infections involves two signaling pathways, Toll and Imd, which both activate members of the transcription factor NF-kappaB family. Here we have studied the global transcriptional response of flies to infection with drosophila C virus. Viral infection induced a set of genes distinct from those regulated by the Toll or Imd pathways and triggered a signal transducer and activator of transcription (STAT) DNA-binding activity. Genetic experiments showed that the Jak kinase Hopscotch was involved in the control of the viral load in infected flies and was required but not sufficient for the induction of some virus-regulated genes. Our results indicate that in addition to Toll and Imd, a third, evolutionary conserved innate immunity pathway functions in drosophila and counters viral infection.}, keywords = {Animals, bioinformatic, DNA-Binding Proteins, Genetic, Genetically Modified, hoffmann, imler, Insect Viruses, Janus Kinase 1, M3i, Male, Oligonucleotide Array Sequence Analysis, Promoter Regions, Protein-Tyrosine Kinases, Signal Transduction, STAT1 Transcription Factor, Trans-Activators}, pubstate = {published}, tppubtype = {article} } The response of drosophila to bacterial and fungal infections involves two signaling pathways, Toll and Imd, which both activate members of the transcription factor NF-kappaB family. Here we have studied the global transcriptional response of flies to infection with drosophila C virus. Viral infection induced a set of genes distinct from those regulated by the Toll or Imd pathways and triggered a signal transducer and activator of transcription (STAT) DNA-binding activity. Genetic experiments showed that the Jak kinase Hopscotch was involved in the control of the viral load in infected flies and was required but not sufficient for the induction of some virus-regulated genes. Our results indicate that in addition to Toll and Imd, a third, evolutionary conserved innate immunity pathway functions in drosophila and counters viral infection. |
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. |
Imler, Jean-Luc; Bulet, Philippe Antimicrobial peptides in Drosophila: structures, activities and gene regulation Article de journal Chemical Immunology and Allergy, 86 , p. 1–21, 2005, ISSN: 1660-2242. Résumé | Liens | BibTeX | Étiquettes: Animals, Antimicrobial Cationic Peptides, Defensins, Gene Expression Regulation, Genes, Glycopeptides, imler, Immunity, Innate, Insect, Insect Proteins, M3i, Molecular Structure, Signal Transduction @article{imler_antimicrobial_2005, title = {Antimicrobial peptides in Drosophila: structures, activities and gene regulation}, author = {Jean-Luc Imler and Philippe Bulet}, doi = {10.1159/000086648}, issn = {1660-2242}, year = {2005}, date = {2005-01-01}, journal = {Chemical Immunology and Allergy}, volume = {86}, pages = {1--21}, abstract = {The production of antimicrobial peptides (AMPs) is an important aspect of host-defence in multicellular organisms. Biochemical analysis of the hemolymph of the fruit-fly Drosophila melanogaster and other Diptera has led to the discovery of eight classes of AMPs. These peptides can be grouped into three families based on their main biological targets, gram-positive bacteria (defensin), gram-negative bacteria (cecropins, drosocin, attacins, diptericin, MPAC), or fungi (drosomycin, metchnikowin). Drosophila AMPs are synthesized by the fat body in response to infection, and secreted into the blood. Most of them can also be induced in surface epithelia in a tissue-specific manner. Finally, some of them are constitutively expressed in defined tissues, such as the salivary glands or the reproductive tract. We review here the structures and activities of these AMPs, as well as the signalling cascades, which lead to their induction upon detection of infectious non-self.}, keywords = {Animals, Antimicrobial Cationic Peptides, Defensins, Gene Expression Regulation, Genes, Glycopeptides, imler, Immunity, Innate, Insect, Insect Proteins, M3i, Molecular Structure, Signal Transduction}, pubstate = {published}, tppubtype = {article} } The production of antimicrobial peptides (AMPs) is an important aspect of host-defence in multicellular organisms. Biochemical analysis of the hemolymph of the fruit-fly Drosophila melanogaster and other Diptera has led to the discovery of eight classes of AMPs. These peptides can be grouped into three families based on their main biological targets, gram-positive bacteria (defensin), gram-negative bacteria (cecropins, drosocin, attacins, diptericin, MPAC), or fungi (drosomycin, metchnikowin). Drosophila AMPs are synthesized by the fat body in response to infection, and secreted into the blood. Most of them can also be induced in surface epithelia in a tissue-specific manner. Finally, some of them are constitutively expressed in defined tissues, such as the salivary glands or the reproductive tract. We review here the structures and activities of these AMPs, as well as the signalling cascades, which lead to their induction upon detection of infectious non-self. |
2004 |
Ferrandon, Dominique; Imler, Jean-Luc; Hoffmann, Jules A Sensing infection in Drosophila: Toll and beyond Article de journal Semin Immunol, 16 , p. 43–53, 2004, ISSN: 1044-5323. Résumé | BibTeX | Étiquettes: Animals, Carrier Proteins/chemistry/immunology/physiology, Cell Surface/immunology/*physiology, Drosophila Proteins/chemistry/immunology/*physiology, Drosophila/genetics/*immunology/microbiology, ferrandon, Fungi/immunology, Gene Expression Regulation, Gram-Negative Bacterial Infections/immunology, Gram-Positive Bacterial Infections/immunology, hoffmann, imler, Immunological, Insect Proteins/chemistry/immunology/physiology, M3i, Models, Non-U.S. Gov't, Receptors, Signal Transduction/immunology/physiology, Support @article{ferrandon_sensing_2004b, title = {Sensing infection in Drosophila: Toll and beyond}, author = {Dominique Ferrandon and Jean-Luc Imler and Jules A Hoffmann}, issn = {1044-5323}, year = {2004}, date = {2004-01-01}, journal = {Semin Immunol}, volume = {16}, pages = {43--53}, abstract = {Drosophila has evolved a potent immune system that is somewhat adapted to the nature of infections through the selective activation of either one of two NF-kappa B-like signalling pathways, the Toll and IMD (Immune deficiency) pathways. In contrast to the mammalian system, the Toll receptor does not act as a pattern recognition receptor (PRR) but as a cytokine receptor. The sensing of microbial infections is achieved by at least four PRRs that belong to two distinct families: the peptidoglycan recognition proteins (PGRPs) and the Gram-negative binding proteins (GNBPs)/beta-glucan recognition proteins (beta GRPs).}, keywords = {Animals, Carrier Proteins/chemistry/immunology/physiology, Cell Surface/immunology/*physiology, Drosophila Proteins/chemistry/immunology/*physiology, Drosophila/genetics/*immunology/microbiology, ferrandon, Fungi/immunology, Gene Expression Regulation, Gram-Negative Bacterial Infections/immunology, Gram-Positive Bacterial Infections/immunology, hoffmann, imler, Immunological, Insect Proteins/chemistry/immunology/physiology, M3i, Models, Non-U.S. Gov't, Receptors, Signal Transduction/immunology/physiology, Support}, pubstate = {published}, tppubtype = {article} } Drosophila has evolved a potent immune system that is somewhat adapted to the nature of infections through the selective activation of either one of two NF-kappa B-like signalling pathways, the Toll and IMD (Immune deficiency) pathways. In contrast to the mammalian system, the Toll receptor does not act as a pattern recognition receptor (PRR) but as a cytokine receptor. The sensing of microbial infections is achieved by at least four PRRs that belong to two distinct families: the peptidoglycan recognition proteins (PGRPs) and the Gram-negative binding proteins (GNBPs)/beta-glucan recognition proteins (beta GRPs). |
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. |
Imler, Jean-Luc; Ferrandon, Dominique; Royet, Julien; Reichhart, Jean-Marc; Hetru, Charles; Hoffmann, Jules A Toll-dependent and Toll-independent immune responses in Drosophila Article de journal Journal of Endotoxin Research, 10 (4), p. 241–246, 2004, ISSN: 0968-0519. Résumé | Liens | BibTeX | Étiquettes: Acute-Phase Proteins, Animals, Blood Proteins, Cell Surface, ferrandon, hoffmann, imler, Insect Proteins, M3i, Membrane Glycoproteins, Receptors, reichhart, Toll-Like Receptor 5, Toll-Like Receptors, Up-Regulation @article{imler_toll-dependent_2004, title = {Toll-dependent and Toll-independent immune responses in Drosophila}, author = {Jean-Luc Imler and Dominique Ferrandon and Julien Royet and Jean-Marc Reichhart and Charles Hetru and Jules A Hoffmann}, doi = {10.1179/096805104225005887}, issn = {0968-0519}, year = {2004}, date = {2004-01-01}, journal = {Journal of Endotoxin Research}, volume = {10}, number = {4}, pages = {241--246}, abstract = {The multifaceted response of the fruitfly Drosophila melanogaster to infection by a wide range of microbes is complex and remarkably efficient. Its most prominent aspect is the immune-inducible expression of a set of potent antimicrobial peptides. Genetic analysis of the regulation of the genes encoding these peptides has led to the identification of the receptor Toll as an essential component of the fly's host defense system. In addition, these studies have revealed that the response to Gram-negative bacterial infections involves Toll-independent mechanisms, and that the sensing of infection involves two structurally distinct sets of molecules--the PGRPs and the GNBPs/betaGRPs.}, keywords = {Acute-Phase Proteins, Animals, Blood Proteins, Cell Surface, ferrandon, hoffmann, imler, Insect Proteins, M3i, Membrane Glycoproteins, Receptors, reichhart, Toll-Like Receptor 5, Toll-Like Receptors, Up-Regulation}, pubstate = {published}, tppubtype = {article} } The multifaceted response of the fruitfly Drosophila melanogaster to infection by a wide range of microbes is complex and remarkably efficient. Its most prominent aspect is the immune-inducible expression of a set of potent antimicrobial peptides. Genetic analysis of the regulation of the genes encoding these peptides has led to the identification of the receptor Toll as an essential component of the fly's host defense system. In addition, these studies have revealed that the response to Gram-negative bacterial infections involves Toll-independent mechanisms, and that the sensing of infection involves two structurally distinct sets of molecules--the PGRPs and the GNBPs/betaGRPs. |
2003 |
Weber, Alexander N R; Tauszig-Delamasure, Servane; Hoffmann, Jules A; Lelièvre, Eric; Gascan, Hugues; Ray, Keith P; Morse, Mary A; Imler, Jean-Luc; Gay, Nicholas J Binding of the Drosophila cytokine Spätzle to Toll is direct and establishes signaling Article de journal Nature Immunology, 4 (8), p. 794–800, 2003, ISSN: 1529-2908. Résumé | Liens | BibTeX | Étiquettes: Animals, Cell Surface, hoffmann, imler, Insect Proteins, M3i, Protein Binding, Protein Structure, Receptors, Signal Transduction, Tertiary, Toll-Like Receptors @article{weber_binding_2003, title = {Binding of the Drosophila cytokine Spätzle to Toll is direct and establishes signaling}, author = {Alexander N R Weber and Servane Tauszig-Delamasure and Jules A Hoffmann and Eric Lelièvre and Hugues Gascan and Keith P Ray and Mary A Morse and Jean-Luc Imler and Nicholas J Gay}, doi = {10.1038/ni955}, issn = {1529-2908}, year = {2003}, date = {2003-08-01}, journal = {Nature Immunology}, volume = {4}, number = {8}, pages = {794--800}, abstract = {The extracellular protein Spätzle is required for activation of the Toll signaling pathway in the embryonic development and innate immune defense of Drosophila. Spätzle is synthesized as a pro-protein and is processed to a functional form by a serine protease. We show here that the mature form of Spätzle triggers a Toll-dependent immune response after injection into the hemolymph of flies. Spätzle specifically bound to Drosophila cells and to Cos-7 cells expressing Toll. Furthermore, in vitro experiments showed that the mature form of Spätzle bound to the Toll ectodomain with high affinity and with a stoichiometry of one Spätzle dimer to two receptors. The Spätzle pro-protein was inactive in all these assays, indicating that the pro-domain sequence, which is natively unstructured, acts to prevent interaction of the cytokine and its receptor Toll. These results show that, in contrast to the human Toll-like receptors, Drosophila Toll requires only an endogenous protein ligand for activation and signaling.}, keywords = {Animals, Cell Surface, hoffmann, imler, Insect Proteins, M3i, Protein Binding, Protein Structure, Receptors, Signal Transduction, Tertiary, Toll-Like Receptors}, pubstate = {published}, tppubtype = {article} } The extracellular protein Spätzle is required for activation of the Toll signaling pathway in the embryonic development and innate immune defense of Drosophila. Spätzle is synthesized as a pro-protein and is processed to a functional form by a serine protease. We show here that the mature form of Spätzle triggers a Toll-dependent immune response after injection into the hemolymph of flies. Spätzle specifically bound to Drosophila cells and to Cos-7 cells expressing Toll. Furthermore, in vitro experiments showed that the mature form of Spätzle bound to the Toll ectodomain with high affinity and with a stoichiometry of one Spätzle dimer to two receptors. The Spätzle pro-protein was inactive in all these assays, indicating that the pro-domain sequence, which is natively unstructured, acts to prevent interaction of the cytokine and its receptor Toll. These results show that, in contrast to the human Toll-like receptors, Drosophila Toll requires only an endogenous protein ligand for activation and signaling. |
Bilak, Hana; Tauszig-Delamasure, S; Imler, Jean-Luc Toll and Toll-like receptors in Drosophila Article de journal Biochemical Society Transactions, 31 (Pt 3), p. 648–651, 2003, ISSN: 0300-5127. Résumé | Liens | BibTeX | Étiquettes: Animals, Biological Evolution, Cell Surface, Fungi, Genome, Gram-Negative Bacteria, Gram-Positive Bacteria, imler, M3i, Membrane Glycoproteins, Receptors, Toll-Like Receptor 5, Toll-Like Receptors @article{bilak_toll_2003, title = {Toll and Toll-like receptors in Drosophila}, author = {Hana Bilak and S Tauszig-Delamasure and Jean-Luc Imler}, doi = {10.1042/}, issn = {0300-5127}, year = {2003}, date = {2003-06-01}, journal = {Biochemical Society Transactions}, volume = {31}, number = {Pt 3}, pages = {648--651}, abstract = {The Drosophila Toll receptor controls the immune response to Gram-positive bacteria and fungi by activating a signalling pathway partially conserved throughout evolution. The Drosophila genome encodes eight additional Toll-related receptors, most of which appear to carry out developmental rather than immune functions. One exception may be Toll-9, which shares structural and functional similarities with mammalian TLRs.}, keywords = {Animals, Biological Evolution, Cell Surface, Fungi, Genome, Gram-Negative Bacteria, Gram-Positive Bacteria, imler, M3i, Membrane Glycoproteins, Receptors, Toll-Like Receptor 5, Toll-Like Receptors}, pubstate = {published}, tppubtype = {article} } The Drosophila Toll receptor controls the immune response to Gram-positive bacteria and fungi by activating a signalling pathway partially conserved throughout evolution. The Drosophila genome encodes eight additional Toll-related receptors, most of which appear to carry out developmental rather than immune functions. One exception may be Toll-9, which shares structural and functional similarities with mammalian TLRs. |