Publications
Amino Acid Anti-Bacterial Agents Base Sequence Cell Surface Defensins Ecdysone Escherichia coli Female Gene Expression Regulation Genes Genetic Grasshoppers Hemolymph Humans Immunity Innate Insect Insect Hormones Insect Proteins Larva Membrane Glycoproteins Models Molecular Mutation Peptides Receptors RNA Sequence Homology Signal Transduction Toll-Like Receptors
2014 |
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Articles de journaux |
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| 22. | Bonnay, François; Nguyen, Xuan-Hung; Cohen-Berros, Eva; Troxler, Laurent; Batsche, Eric; Camonis, Jacques; Takeuchi, Osamu; Reichhart, Jean-Marc; Matt, Nicolas Akirin specifies NF-κB selectivity of Drosophila innate immune response via chromatin remodeling Article de journal EMBO J., 33 (20), p. 2349–2362, 2014, ISSN: 1460-2075. Résumé | Liens | BibTeX | Étiquettes: bioinformatic, Cell Cycle Proteins, Chromatin Assembly and Disassembly, chromatin remodeling, DNA-Binding Proteins, Female, Genetic, Immunity, Innate, Innate immune response, Male, Mutation, NF-kappa B, NF‐κB, Promoter Regions, Proteomics, Trans-Activators, Transcription Factors, Transcriptional Activation, Two-Hybrid System Techniques @article{bonnay_akirin_2014, title = {Akirin specifies NF-κB selectivity of Drosophila innate immune response via chromatin remodeling}, author = { François Bonnay and Xuan-Hung Nguyen and Eva Cohen-Berros and Laurent Troxler and Eric Batsche and Jacques Camonis and Osamu Takeuchi and Jean-Marc Reichhart and Nicolas Matt}, doi = {10.15252/embj.201488456}, issn = {1460-2075}, year = {2014}, date = {2014-10-01}, journal = {EMBO J.}, volume = {33}, number = {20}, pages = {2349--2362}, abstract = {The network of NF-κB-dependent transcription that activates both pro- and anti-inflammatory genes in mammals is still unclear. As NF-κB factors are evolutionarily conserved, we used Drosophila to understand this network. The NF-κB transcription factor Relish activates effector gene expression following Gram-negative bacterial immune challenge. Here, we show, using a genome-wide approach, that the conserved nuclear protein Akirin is a NF-κB co-factor required for the activation of a subset of Relish-dependent genes correlating with the presence of H3K4ac epigenetic marks. A large-scale unbiased proteomic analysis revealed that Akirin orchestrates NF-κB transcriptional selectivity through the recruitment of the Osa-containing-SWI/SNF-like Brahma complex (BAP). Immune challenge in Drosophila shows that Akirin is required for the transcription of a subset of effector genes, but dispensable for the transcription of genes that are negative regulators of the innate immune response. Therefore, Akirins act as molecular selectors specifying the choice between subsets of NF-κB target genes. The discovery of this mechanism, conserved in mammals, paves the way for the establishment of more specific and less toxic anti-inflammatory drugs targeting pro-inflammatory genes.}, keywords = {bioinformatic, Cell Cycle Proteins, Chromatin Assembly and Disassembly, chromatin remodeling, DNA-Binding Proteins, Female, Genetic, Immunity, Innate, Innate immune response, Male, Mutation, NF-kappa B, NF‐κB, Promoter Regions, Proteomics, Trans-Activators, Transcription Factors, Transcriptional Activation, Two-Hybrid System Techniques}, pubstate = {published}, tppubtype = {article} } The network of NF-κB-dependent transcription that activates both pro- and anti-inflammatory genes in mammals is still unclear. As NF-κB factors are evolutionarily conserved, we used Drosophila to understand this network. The NF-κB transcription factor Relish activates effector gene expression following Gram-negative bacterial immune challenge. Here, we show, using a genome-wide approach, that the conserved nuclear protein Akirin is a NF-κB co-factor required for the activation of a subset of Relish-dependent genes correlating with the presence of H3K4ac epigenetic marks. A large-scale unbiased proteomic analysis revealed that Akirin orchestrates NF-κB transcriptional selectivity through the recruitment of the Osa-containing-SWI/SNF-like Brahma complex (BAP). Immune challenge in Drosophila shows that Akirin is required for the transcription of a subset of effector genes, but dispensable for the transcription of genes that are negative regulators of the innate immune response. Therefore, Akirins act as molecular selectors specifying the choice between subsets of NF-κB target genes. The discovery of this mechanism, conserved in mammals, paves the way for the establishment of more specific and less toxic anti-inflammatory drugs targeting pro-inflammatory genes. |
2013 |
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Articles de journaux |
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| 21. | Ayyaz, Arshad; Giammarinaro, Philippe; Liégeois, Samuel; Lestradet, Matthieu; Ferrandon, Dominique A negative role for MyD88 in the resistance to starvation as revealed in an intestinal infection of Drosophila melanogaster with the Gram-positive bacterium Staphylococcus xylosus Article de journal Immunobiology, 218 (4), p. 635–644, 2013, ISSN: 1878-3279. Résumé | Liens | BibTeX | Étiquettes: Adaptor Proteins, Animal, Antigens, Differentiation, Disease Models, Immunity, Immunologic, Innate, Intestinal Diseases, Mucosal, Mutation, Receptors, Signal Transducing, Staphylococcal Infections, Staphylococcus, Starvation, Toll-Like Receptors @article{ayyaz_negative_2013b, title = {A negative role for MyD88 in the resistance to starvation as revealed in an intestinal infection of Drosophila melanogaster with the Gram-positive bacterium Staphylococcus xylosus}, author = { Arshad Ayyaz and Philippe Giammarinaro and Samuel Liégeois and Matthieu Lestradet and Dominique Ferrandon}, doi = {10.1016/j.imbio.2012.07.027}, issn = {1878-3279}, year = {2013}, date = {2013-01-01}, journal = {Immunobiology}, volume = {218}, number = {4}, pages = {635--644}, abstract = {Drosophila melanogaster is a useful model to investigate mucosal immunity. The immune response to intestinal infections is mediated partly by the Immune deficiency (IMD) pathway, which only gets activated by a type of peptidoglycan lacking in several medically important Gram-positive bacterial species such as Staphylococcus. Thus, the intestinal host defense against such bacterial strains remains poorly known. Here, we have used Staphylococcus xylosus to develop a model of intestinal infections by Gram-positive bacteria. S. xylosus behaves as an opportunistic pathogen in a septic injury model, being able to kill only flies immunodeficient either for the Toll pathway or the cellular response. When ingested, it is controlled by IMD-independent host intestinal defenses, yet flies eventually die. Having excluded an overreaction of the immune response and the action of toxins, we find that flies actually succumb to starvation, likely as a result of a competition for sucrose between the bacteria and the flies. Fat stores of wild-type flies are severely reduced within a day, a period when sucrose is not yet exhausted in the feeding solution. Interestingly, the Toll pathway mutant MyD88 is more resistant to the ingestion of S. xylosus and to starvation than wild-type flies. MyD88 flies do not rapidly deplete their fat stores when starved, in contrast to wild-type flies. Thus, we have uncovered a novel function of MyD88 in the regulation of metabolism that appears to be independent of its known roles in immunity and development.}, keywords = {Adaptor Proteins, Animal, Antigens, Differentiation, Disease Models, Immunity, Immunologic, Innate, Intestinal Diseases, Mucosal, Mutation, Receptors, Signal Transducing, Staphylococcal Infections, Staphylococcus, Starvation, Toll-Like Receptors}, pubstate = {published}, tppubtype = {article} } Drosophila melanogaster is a useful model to investigate mucosal immunity. The immune response to intestinal infections is mediated partly by the Immune deficiency (IMD) pathway, which only gets activated by a type of peptidoglycan lacking in several medically important Gram-positive bacterial species such as Staphylococcus. Thus, the intestinal host defense against such bacterial strains remains poorly known. Here, we have used Staphylococcus xylosus to develop a model of intestinal infections by Gram-positive bacteria. S. xylosus behaves as an opportunistic pathogen in a septic injury model, being able to kill only flies immunodeficient either for the Toll pathway or the cellular response. When ingested, it is controlled by IMD-independent host intestinal defenses, yet flies eventually die. Having excluded an overreaction of the immune response and the action of toxins, we find that flies actually succumb to starvation, likely as a result of a competition for sucrose between the bacteria and the flies. Fat stores of wild-type flies are severely reduced within a day, a period when sucrose is not yet exhausted in the feeding solution. Interestingly, the Toll pathway mutant MyD88 is more resistant to the ingestion of S. xylosus and to starvation than wild-type flies. MyD88 flies do not rapidly deplete their fat stores when starved, in contrast to wild-type flies. Thus, we have uncovered a novel function of MyD88 in the regulation of metabolism that appears to be independent of its known roles in immunity and development. |
2011 |
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Articles de journaux |
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| 20. | Limmer, Stefanie; Haller, Samantha; Drenkard, Eliana; Lee, Janice; Yu, Shen; Kocks, Christine; Ausubel, Frederick M; Ferrandon, Dominique Pseudomonas aeruginosa RhlR is required to neutralize the cellular immune response in a Drosophila melanogaster oral infection model Article de journal Proc. Natl. Acad. Sci. U.S.A., 108 (42), p. 17378–17383, 2011, ISSN: 1091-6490. Résumé | Liens | BibTeX | Étiquettes: Animal, Bacteremia, Bacterial Proteins, Cellular, Disease Models, Genes, Genetically Modified, Hemolymph, Host-Pathogen Interactions, Immunity, Insect, Mutation, Oral, Pseudomonas aeruginosa, Pseudomonas Infections, Quorum Sensing, Trans-Activators, Viral, Virulence @article{limmer_pseudomonas_2011b, title = {Pseudomonas aeruginosa RhlR is required to neutralize the cellular immune response in a Drosophila melanogaster oral infection model}, author = { Stefanie Limmer and Samantha Haller and Eliana Drenkard and Janice Lee and Shen Yu and Christine Kocks and Frederick M. Ausubel and Dominique Ferrandon}, doi = {10.1073/pnas.1114907108}, issn = {1091-6490}, year = {2011}, date = {2011-10-01}, journal = {Proc. Natl. Acad. Sci. U.S.A.}, volume = {108}, number = {42}, pages = {17378--17383}, abstract = {An in-depth mechanistic understanding of microbial infection necessitates a molecular dissection of host-pathogen relationships. Both Drosophila melanogaster and Pseudomonas aeruginosa have been intensively studied. Here, we analyze the infection of D. melanogaster by P. aeruginosa by using mutants in both host and pathogen. We show that orally ingested P. aeruginosa crosses the intestinal barrier and then proliferates in the hemolymph, thereby causing the infected flies to die of bacteremia. Host defenses against ingested P. aeruginosa included an immune deficiency (IMD) response in the intestinal epithelium, systemic Toll and IMD pathway responses, and a cellular immune response controlling bacteria in the hemocoel. Although the observed cellular and intestinal immune responses appeared to act throughout the course of the infection, there was a late onset of the systemic IMD and Toll responses. In this oral infection model, P. aeruginosa PA14 did not require its type III secretion system or other well-studied virulence factors such as the two-component response regulator GacA or the protease AprA for virulence. In contrast, the quorum-sensing transcription factor RhlR, but surprisingly not LasR, played a key role in counteracting the cellular immune response against PA14, possibly at an early stage when only a few bacteria are present in the hemocoel. These results illustrate the power of studying infection from the dual perspective of host and pathogen by revealing that RhlR plays a more complex role during pathogenesis than previously appreciated.}, keywords = {Animal, Bacteremia, Bacterial Proteins, Cellular, Disease Models, Genes, Genetically Modified, Hemolymph, Host-Pathogen Interactions, Immunity, Insect, Mutation, Oral, Pseudomonas aeruginosa, Pseudomonas Infections, Quorum Sensing, Trans-Activators, Viral, Virulence}, pubstate = {published}, tppubtype = {article} } An in-depth mechanistic understanding of microbial infection necessitates a molecular dissection of host-pathogen relationships. Both Drosophila melanogaster and Pseudomonas aeruginosa have been intensively studied. Here, we analyze the infection of D. melanogaster by P. aeruginosa by using mutants in both host and pathogen. We show that orally ingested P. aeruginosa crosses the intestinal barrier and then proliferates in the hemolymph, thereby causing the infected flies to die of bacteremia. Host defenses against ingested P. aeruginosa included an immune deficiency (IMD) response in the intestinal epithelium, systemic Toll and IMD pathway responses, and a cellular immune response controlling bacteria in the hemocoel. Although the observed cellular and intestinal immune responses appeared to act throughout the course of the infection, there was a late onset of the systemic IMD and Toll responses. In this oral infection model, P. aeruginosa PA14 did not require its type III secretion system or other well-studied virulence factors such as the two-component response regulator GacA or the protease AprA for virulence. In contrast, the quorum-sensing transcription factor RhlR, but surprisingly not LasR, played a key role in counteracting the cellular immune response against PA14, possibly at an early stage when only a few bacteria are present in the hemocoel. These results illustrate the power of studying infection from the dual perspective of host and pathogen by revealing that RhlR plays a more complex role during pathogenesis than previously appreciated. |
| 19. | Aoun, Richard Bou; Hetru, Charles; Troxler, Laurent; Doucet, Daniel; Ferrandon, Dominique; Matt, Nicolas Analysis of thioester-containing proteins during the innate immune response of Drosophila melanogaster Article de journal J Innate Immun, 3 (1), p. 52–64, 2011, ISSN: 1662-8128. Résumé | Liens | BibTeX | Étiquettes: bioinformatic, DNA, Evolution, Gene Expression Regulation, Hemocytes, Immunity, In Situ Hybridization, Innate, Molecular, Mutation, Phylogeny, Sequence Analysis @article{bou_aoun_analysis_2011, title = {Analysis of thioester-containing proteins during the innate immune response of Drosophila melanogaster}, author = { Richard Bou Aoun and Charles Hetru and Laurent Troxler and Daniel Doucet and Dominique Ferrandon and Nicolas Matt}, doi = {10.1159/000321554}, issn = {1662-8128}, year = {2011}, date = {2011-01-01}, journal = {J Innate Immun}, volume = {3}, number = {1}, pages = {52--64}, abstract = {Thioester-containing proteins (TEPs) are conserved proteins among insects that are thought to be involved in innate immunity. In Drosophila, the Tep family is composed of 6 genes named Tep1-Tep6. In this study, we investigated the phylogeny, expression pattern and roles of these genes in the host defense of Drosophila. Protostomian Tep genes are clustered in 3 distinct branches, 1 of which is specific to mosquitoes. Most D. melanogaster Tep genes are expressed in hemocytes, can be induced in the fat body, and are expressed in specific regions of the hypodermis. This expression pattern is consistent with a role in innate immunity. However, we find that TEP1, TEP2, and TEP4 are not strictly required in the body cavity to fight several bacterial and fungal infections. One possibility is that Drosophila TEPs act redundantly or that their absence can be compensated by other components of the immune response. TEPs may thus provide a subtle selective advantage during evolution. Alternatively, they may be required in host defense against specific as yet unidentified natural pathogens of Drosophila.}, keywords = {bioinformatic, DNA, Evolution, Gene Expression Regulation, Hemocytes, Immunity, In Situ Hybridization, Innate, Molecular, Mutation, Phylogeny, Sequence Analysis}, pubstate = {published}, tppubtype = {article} } Thioester-containing proteins (TEPs) are conserved proteins among insects that are thought to be involved in innate immunity. In Drosophila, the Tep family is composed of 6 genes named Tep1-Tep6. In this study, we investigated the phylogeny, expression pattern and roles of these genes in the host defense of Drosophila. Protostomian Tep genes are clustered in 3 distinct branches, 1 of which is specific to mosquitoes. Most D. melanogaster Tep genes are expressed in hemocytes, can be induced in the fat body, and are expressed in specific regions of the hypodermis. This expression pattern is consistent with a role in innate immunity. However, we find that TEP1, TEP2, and TEP4 are not strictly required in the body cavity to fight several bacterial and fungal infections. One possibility is that Drosophila TEPs act redundantly or that their absence can be compensated by other components of the immune response. TEPs may thus provide a subtle selective advantage during evolution. Alternatively, they may be required in host defense against specific as yet unidentified natural pathogens of Drosophila. |
2007 |
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Articles de journaux |
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| 18. | 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: Antiviral Agents, Disease Susceptibility, Drug Resistance, Eukaryotic Cells, Humans, Immunity, 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 = {Antiviral Agents, Disease Susceptibility, Drug Resistance, Eukaryotic Cells, Humans, Immunity, Mutation, Viral, Virus Diseases, Viruses}, pubstate = {published}, tppubtype = {article} } As machines that reprogramme eukaryotic cells to suit their own purposes, viruses present a difficult problem for multicellular hosts, and indeed, have become one of the central pre-occupations of the immune system. Unable to permanently outpace individual viruses in an evolutionary footrace, higher eukaryotes have evolved broadly active mechanisms with which to sense viruses and suppress their proliferation. These mechanisms have recently been elucidated by a combination of forward and reverse genetic methods. Some of these mechanisms are clearly ancient, whereas others are relatively new. All are remarkably adept at discriminating self from non-self, and allow the host to cope with what might seem an impossible predicament. |
2006 |
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Articles de journaux |
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| 17. | 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, Antigens, Biological, Body Patterning, Cell Membrane, Differentiation, Dimerization, DNA-Binding Proteins, Embryo, Epistasis, Genetic, Immunity, Immunologic, Innate, 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, Antigens, Biological, Body Patterning, Cell Membrane, Differentiation, Dimerization, DNA-Binding Proteins, Embryo, Epistasis, Genetic, Immunity, Immunologic, Innate, 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. |
| 16. | 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: Genetically Modified, 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 = {Genetically Modified, 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. |
| 15. | Leclerc, Vincent; Pelte, Nadège ; Chamy, Laure El ; Martinelli, Cosimo ; Ligoxygakis, Petros ; Hoffmann, Jules A; Reichhart, Jean-Marc Prophenoloxidase activation is not required for survival to microbial infections in Drosophila Article de journal EMBO Rep., 7 (2), p. 231–235, 2006, ISSN: 1469-221X. Résumé | Liens | BibTeX | Étiquettes: Bacterial Infections, Catechol Oxidase, Enzyme Activation, Enzyme Precursors, Gram-Negative Bacteria, Gram-Positive Bacteria, Hemolymph, Immunity, Innate, Mutation, Survival Rate @article{leclerc_prophenoloxidase_2006, title = {Prophenoloxidase activation is not required for survival to microbial infections in Drosophila}, author = { Vincent Leclerc and Nadège Pelte and Laure El Chamy and Cosimo Martinelli and Petros Ligoxygakis and Jules A. Hoffmann and Jean-Marc Reichhart}, doi = {10.1038/sj.embor.7400592}, issn = {1469-221X}, year = {2006}, date = {2006-02-01}, journal = {EMBO Rep.}, volume = {7}, number = {2}, pages = {231--235}, abstract = {The antimicrobial defence of Drosophila relies on cellular and humoral processes, of which the inducible synthesis of antimicrobial peptides has attracted interest in recent years. Another potential line of defence is the activation, by a proteolytic cascade, of phenoloxidase, which leads to the production of quinones and melanin. However, in spite of several publications on this subject, the contribution of phenoloxidase activation to resistance to infections has not been established under appropriate in vivo conditions. Here, we have isolated the first Drosophila mutant for a prophenoloxidase-activating enzyme (PAE1). In contrast to wild-type flies, PAE1 mutants fail to activate phenoloxidase in the haemolymph following microbial challenge. Surprisingly, we find that these mutants are as resistant to infections as wild-type flies, in the total absence of circulating phenoloxidase activity. This raises the question with regard to the precise function of phenoloxidase activation in defence, if any.}, keywords = {Bacterial Infections, Catechol Oxidase, Enzyme Activation, Enzyme Precursors, Gram-Negative Bacteria, Gram-Positive Bacteria, Hemolymph, Immunity, Innate, Mutation, Survival Rate}, pubstate = {published}, tppubtype = {article} } The antimicrobial defence of Drosophila relies on cellular and humoral processes, of which the inducible synthesis of antimicrobial peptides has attracted interest in recent years. Another potential line of defence is the activation, by a proteolytic cascade, of phenoloxidase, which leads to the production of quinones and melanin. However, in spite of several publications on this subject, the contribution of phenoloxidase activation to resistance to infections has not been established under appropriate in vivo conditions. Here, we have isolated the first Drosophila mutant for a prophenoloxidase-activating enzyme (PAE1). In contrast to wild-type flies, PAE1 mutants fail to activate phenoloxidase in the haemolymph following microbial challenge. Surprisingly, we find that these mutants are as resistant to infections as wild-type flies, in the total absence of circulating phenoloxidase activity. This raises the question with regard to the precise function of phenoloxidase activation in defence, if any. |
2004 |
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Articles de journaux |
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| 14. | Bischoff, Vincent; Vignal, Cécile; Boneca, Ivo G; Michel, Tatiana; Hoffmann, Jules A; Royet, Julien Function of the drosophila pattern-recognition receptor PGRP-SD in the detection of Gram-positive bacteria Article de journal Nat. Immunol., 5 (11), p. 1175–1180, 2004, ISSN: 1529-2908. Résumé | Liens | BibTeX | Étiquettes: Carrier Proteins, Cell Surface, Gram-Positive Bacteria, Gram-Positive Bacterial Infections, Mutation, Mycoses, Receptors, Staphylococcus aureus, Toll-Like Receptors @article{bischoff_function_2004, title = {Function of the drosophila pattern-recognition receptor PGRP-SD in the detection of Gram-positive bacteria}, author = { Vincent Bischoff and Cécile Vignal and Ivo G. Boneca and Tatiana Michel and Jules A. Hoffmann and Julien Royet}, doi = {10.1038/ni1123}, issn = {1529-2908}, year = {2004}, date = {2004-11-01}, journal = {Nat. Immunol.}, volume = {5}, number = {11}, pages = {1175--1180}, abstract = {The activation of an immune response requires recognition of microorganisms by host receptors. In drosophila, detection of Gram-positive bacteria is mediated by cooperation between the peptidoglycan-recognition protein-SA (PGRP-SA) and Gram-negative binding protein 1 (GNBP1) proteins. Here we show that some Gram-positive bacterial species activate an immune response in a PGRP-SA- and GNBP1-independent manner, indicating that alternative receptors exist. Consistent with this, we noted that PGRP-SD mutants were susceptible to some Gram-positive bacteria and that a loss-of-function mutation in PGRP-SD severely exacerbated the PGRP-SA and GNBP1 mutant phenotypes. These data indicate that PGRP-SD can function as a receptor for Gram-positive bacteria and shows partial redundancy with the PGRP-SA-GNBP1 complex.}, keywords = {Carrier Proteins, Cell Surface, Gram-Positive Bacteria, Gram-Positive Bacterial Infections, Mutation, Mycoses, Receptors, Staphylococcus aureus, Toll-Like Receptors}, pubstate = {published}, tppubtype = {article} } The activation of an immune response requires recognition of microorganisms by host receptors. In drosophila, detection of Gram-positive bacteria is mediated by cooperation between the peptidoglycan-recognition protein-SA (PGRP-SA) and Gram-negative binding protein 1 (GNBP1) proteins. Here we show that some Gram-positive bacterial species activate an immune response in a PGRP-SA- and GNBP1-independent manner, indicating that alternative receptors exist. Consistent with this, we noted that PGRP-SD mutants were susceptible to some Gram-positive bacteria and that a loss-of-function mutation in PGRP-SD severely exacerbated the PGRP-SA and GNBP1 mutant phenotypes. These data indicate that PGRP-SD can function as a receptor for Gram-positive bacteria and shows partial redundancy with the PGRP-SA-GNBP1 complex. |
2003 |
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| 13. | Gobert, Vanessa; Gottar, Marie; Matskevich, Alexey A; Rutschmann, Sophie; Royet, Julien; Belvin, Marcia; Hoffmann, Jules A; Ferrandon, Dominique Dual activation of the Drosophila toll pathway by two pattern recognition receptors Article de journal Science, 302 (5653), p. 2126–2130, 2003, ISSN: 1095-9203. Résumé | Liens | BibTeX | Étiquettes: Carrier Proteins, Cell Surface, DNA Transposable Elements, Gene Expression, Genes, Gram-Negative Bacteria, Gram-Positive Bacteria, Hemolymph, Hypocreales, Insect, Insect Proteins, Mutation, Phenotype, Receptors, Serine Endopeptidases, Toll-Like Receptors @article{gobert_dual_2003, title = {Dual activation of the Drosophila toll pathway by two pattern recognition receptors}, author = { Vanessa Gobert and Marie Gottar and Alexey A. Matskevich and Sophie Rutschmann and Julien Royet and Marcia Belvin and Jules A. Hoffmann and Dominique Ferrandon}, doi = {10.1126/science.1085432}, issn = {1095-9203}, year = {2003}, date = {2003-12-01}, journal = {Science}, volume = {302}, number = {5653}, pages = {2126--2130}, abstract = {The Toll-dependent defense against Gram-positive bacterial infections in Drosophila is mediated through the peptidoglycan recognition protein SA (PGRP-SA). A mutation termed osiris disrupts the Gram-negative binding protein 1 (GNBP1) gene and leads to compromised survival of mutant flies after Gram-positive infections, but not after fungal or Gram-negative bacterial challenge. Our results demonstrate that GNBP1 and PGRP-SA can jointly activate the Toll pathway. The potential for a combination of distinct proteins to mediate detection of infectious nonself in the fly will refine the concept of pattern recognition in insects.}, keywords = {Carrier Proteins, Cell Surface, DNA Transposable Elements, Gene Expression, Genes, Gram-Negative Bacteria, Gram-Positive Bacteria, Hemolymph, Hypocreales, Insect, Insect Proteins, Mutation, Phenotype, Receptors, Serine Endopeptidases, Toll-Like Receptors}, pubstate = {published}, tppubtype = {article} } The Toll-dependent defense against Gram-positive bacterial infections in Drosophila is mediated through the peptidoglycan recognition protein SA (PGRP-SA). A mutation termed osiris disrupts the Gram-negative binding protein 1 (GNBP1) gene and leads to compromised survival of mutant flies after Gram-positive infections, but not after fungal or Gram-negative bacterial challenge. Our results demonstrate that GNBP1 and PGRP-SA can jointly activate the Toll pathway. The potential for a combination of distinct proteins to mediate detection of infectious nonself in the fly will refine the concept of pattern recognition in insects. |
| 12. | Kurz, Léopold C; Chauvet, Sophie; Andrès, Emmanuel; Aurouze, Marianne; Vallet, Isabelle; Michel, Gérard P F; Uh, Mitch; Celli, Jean; Filloux, Alain; Bentzmann, Sophie De; Steinmetz, Ivo; Hoffmann, Jules A; Finlay, Brett B; Gorvel, Jean-Pierre; Ferrandon, Dominique; Ewbank, Jonathan J Virulence factors of the human opportunistic pathogen Serratia marcescens identified by in vivo screening Article de journal Embo J, 22 , p. 1451–60, 2003, ISBN: 0261-4189. Résumé | Liens | BibTeX | Étiquettes: *Virulence, Animal, Caenorhabditis elegans/*microbiology, Mutation, Non-U.S. Gov't, Serratia marcescens/genetics/*pathogenicity, Support @article{kurz_virulence_2003b, title = {Virulence factors of the human opportunistic pathogen Serratia marcescens identified by in vivo screening}, author = {C. Léopold Kurz and Sophie Chauvet and Emmanuel Andrès and Marianne Aurouze and Isabelle Vallet and Gérard P. F. Michel and Mitch Uh and Jean Celli and Alain Filloux and Sophie De Bentzmann and Ivo Steinmetz and Jules A. Hoffmann and B. Brett Finlay and Jean-Pierre Gorvel and Dominique Ferrandon and Jonathan J. Ewbank}, doi = {10.1093/emboj/cdg159}, isbn = {0261-4189}, year = {2003}, date = {2003-04-01}, journal = {Embo J}, volume = {22}, pages = {1451--60}, abstract = {The human opportunistic pathogen Serratia marcescens is a bacterium with a broad host range, and represents a growing problem for public health. Serratia marcescens kills Caenorhabditis elegans after colonizing the nematode's intestine. We used C.elegans to screen a bank of transposon-induced S.marcescens mutants and isolated 23 clones with an attenuated virulence. Nine of the selected bacterial clones also showed a reduced virulence in an insect model of infection. Of these, three exhibited a reduced cytotoxicity in vitro, and among them one was also markedly attenuated in its virulence in a murine lung infection model. For 21 of the 23 mutants, the transposon insertion site was identified. This revealed that among the genes necessary for full in vivo virulence are those that function in lipopolysaccharide (LPS) biosynthesis, iron uptake and hemolysin production. Using this system we also identified novel conserved virulence factors required for Pseudomonas aeruginosa pathogenicity. This study extends the utility of C.elegans as an in vivo model for the study of bacterial virulence and advances the molecular understanding of S.marcescens pathogenicity.}, keywords = {*Virulence, Animal, Caenorhabditis elegans/*microbiology, Mutation, Non-U.S. Gov't, Serratia marcescens/genetics/*pathogenicity, Support}, pubstate = {published}, tppubtype = {article} } The human opportunistic pathogen Serratia marcescens is a bacterium with a broad host range, and represents a growing problem for public health. Serratia marcescens kills Caenorhabditis elegans after colonizing the nematode's intestine. We used C.elegans to screen a bank of transposon-induced S.marcescens mutants and isolated 23 clones with an attenuated virulence. Nine of the selected bacterial clones also showed a reduced virulence in an insect model of infection. Of these, three exhibited a reduced cytotoxicity in vitro, and among them one was also markedly attenuated in its virulence in a murine lung infection model. For 21 of the 23 mutants, the transposon insertion site was identified. This revealed that among the genes necessary for full in vivo virulence are those that function in lipopolysaccharide (LPS) biosynthesis, iron uptake and hemolysin production. Using this system we also identified novel conserved virulence factors required for Pseudomonas aeruginosa pathogenicity. This study extends the utility of C.elegans as an in vivo model for the study of bacterial virulence and advances the molecular understanding of S.marcescens pathogenicity. |
2002 |
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| 11. | Ligoxygakis, Petros; Pelte, Nadège ; Hoffmann, Jules A; Reichhart, Jean-Marc Activation of Drosophila Toll during fungal infection by a blood serine protease Article de journal Science, 297 (5578), p. 114–116, 2002, ISSN: 1095-9203. Résumé | Liens | BibTeX | Étiquettes: Cell Surface, Chromosome Mapping, Escherichia coli, Female, Gene Expression Regulation, Genes, Gram-Positive Cocci, Hemolymph, Hypocreales, Insect, Insect Proteins, Male, Mutation, Protein Sorting Signals, Protein Structure, Receptors, Serine Endopeptidases, Tertiary, Toll-Like Receptors @article{ligoxygakis_activation_2002, title = {Activation of Drosophila Toll during fungal infection by a blood serine protease}, author = { Petros Ligoxygakis and Nadège Pelte and Jules A. Hoffmann and Jean-Marc Reichhart}, doi = {10.1126/science.1072391}, issn = {1095-9203}, year = {2002}, date = {2002-07-01}, journal = {Science}, volume = {297}, number = {5578}, pages = {114--116}, abstract = {Drosophila host defense to fungal and Gram-positive bacterial infection is mediated by the Spaetzle/Toll/cactus gene cassette. It has been proposed that Toll does not function as a pattern recognition receptor per se but is activated through a cleaved form of the cytokine Spaetzle. The upstream events linking infection to the cleavage of Spaetzle have long remained elusive. Here we report the identification of a central component of the fungal activation of Toll. We show that ethylmethane sulfonate-induced mutations in the persephone gene, which encodes a previously unknown serine protease, block induction of the Toll pathway by fungi and resistance to this type of infection.}, keywords = {Cell Surface, Chromosome Mapping, Escherichia coli, Female, Gene Expression Regulation, Genes, Gram-Positive Cocci, Hemolymph, Hypocreales, Insect, Insect Proteins, Male, Mutation, Protein Sorting Signals, Protein Structure, Receptors, Serine Endopeptidases, Tertiary, Toll-Like Receptors}, pubstate = {published}, tppubtype = {article} } Drosophila host defense to fungal and Gram-positive bacterial infection is mediated by the Spaetzle/Toll/cactus gene cassette. It has been proposed that Toll does not function as a pattern recognition receptor per se but is activated through a cleaved form of the cytokine Spaetzle. The upstream events linking infection to the cleavage of Spaetzle have long remained elusive. Here we report the identification of a central component of the fungal activation of Toll. We show that ethylmethane sulfonate-induced mutations in the persephone gene, which encodes a previously unknown serine protease, block induction of the Toll pathway by fungi and resistance to this type of infection. |
| 10. | Gottar, Marie; Gobert, Vanessa; Michel, Tatiana; Belvin, Marcia; Duyk, Geoffrey; Hoffmann, Jules A; Ferrandon, Dominique; Royet, Julien The Drosophila immune response against Gram-negative bacteria is mediated by a peptidoglycan recognition protein Article de journal Nature, 416 , p. 640–644, 2002, ISBN: 0028-0836. Résumé | Liens | BibTeX | Étiquettes: Animal, Anti-Infective Agents/metabolism, Carrier Proteins/biosynthesis/genetics/*immunology, Drosophila melanogaster/genetics/*immunology/*microbiology, Drosophila Proteins/genetics/metabolism, Epistasis, Female, Genes, Genetic, Genetic Predisposition to Disease, Gram-Negative Bacteria/*immunology/physiology, Human, Insect/genetics, Messenger/genetics/metabolism, Mutation, Non-U.S. Gov't, P.H.S., Phenotype, RNA, Signal Transduction, Support, Survival Rate, Transgenes/genetics, U.S. Gov't @article{gottar_drosophila_2002b, title = {The Drosophila immune response against Gram-negative bacteria is mediated by a peptidoglycan recognition protein}, author = {Marie Gottar and Vanessa Gobert and Tatiana Michel and Marcia Belvin and Geoffrey Duyk and Jules A. Hoffmann and Dominique Ferrandon and Julien Royet}, doi = {10.1038/nature734}, isbn = {0028-0836}, year = {2002}, date = {2002-03-01}, journal = {Nature}, volume = {416}, pages = {640--644}, abstract = {The antimicrobial defence of Drosophila relies largely on the challenge-induced synthesis of an array of potent antimicrobial peptides by the fat body. The defence against Gram-positive bacteria and natural fungal infections is mediated by the Toll signalling pathway, whereas defence against Gram-negative bacteria is dependent on the Immune deficiency (IMD) pathway. Loss-of-function mutations in either pathway reduce the resistance to corresponding infections. The link between microbial infections and activation of these two pathways has remained elusive. The Toll pathway is activated by Gram-positive bacteria through a circulating Peptidoglycan recognition protein (PGRP-SA). PGRPs appear to be highly conserved from insects to mammals, and the Drosophila genome contains 13 members. Here we report a mutation in a gene coding for a putative transmembrane protein, PGRP-LC, which reduces survival to Gram-negative sepsis but has no effect on the response to Gram-positive bacteria or natural fungal infections. By genetic epistasis, we demonstrate that PGRP-LC acts upstream of the imd gene. The data on PGRP-SA with respect to the response to Gram-positive infections, together with the present report, indicate that the PGRP family has a principal role in sensing microbial infections in Drosophila.}, keywords = {Animal, Anti-Infective Agents/metabolism, Carrier Proteins/biosynthesis/genetics/*immunology, Drosophila melanogaster/genetics/*immunology/*microbiology, Drosophila Proteins/genetics/metabolism, Epistasis, Female, Genes, Genetic, Genetic Predisposition to Disease, Gram-Negative Bacteria/*immunology/physiology, Human, Insect/genetics, Messenger/genetics/metabolism, Mutation, Non-U.S. Gov't, P.H.S., Phenotype, RNA, Signal Transduction, Support, Survival Rate, Transgenes/genetics, U.S. Gov't}, pubstate = {published}, tppubtype = {article} } The antimicrobial defence of Drosophila relies largely on the challenge-induced synthesis of an array of potent antimicrobial peptides by the fat body. The defence against Gram-positive bacteria and natural fungal infections is mediated by the Toll signalling pathway, whereas defence against Gram-negative bacteria is dependent on the Immune deficiency (IMD) pathway. Loss-of-function mutations in either pathway reduce the resistance to corresponding infections. The link between microbial infections and activation of these two pathways has remained elusive. The Toll pathway is activated by Gram-positive bacteria through a circulating Peptidoglycan recognition protein (PGRP-SA). PGRPs appear to be highly conserved from insects to mammals, and the Drosophila genome contains 13 members. Here we report a mutation in a gene coding for a putative transmembrane protein, PGRP-LC, which reduces survival to Gram-negative sepsis but has no effect on the response to Gram-positive bacteria or natural fungal infections. By genetic epistasis, we demonstrate that PGRP-LC acts upstream of the imd gene. The data on PGRP-SA with respect to the response to Gram-positive infections, together with the present report, indicate that the PGRP family has a principal role in sensing microbial infections in Drosophila. |
2001 |
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| 9. | Michel, T; Reichhart, Jean-Marc ; Hoffmann, Jules A; Royet, Julien Drosophila Toll is activated by Gram-positive bacteria through a circulating peptidoglycan recognition protein Article de journal Nature, 414 (6865), p. 756–759, 2001, ISSN: 0028-0836. Résumé | Liens | BibTeX | Étiquettes: Amino Acid, Anti-Bacterial Agents, Anti-Infective Agents, Bacillus thuringiensis, Carrier Proteins, Cell Surface, Chromosome Mapping, Enterococcus faecalis, Fungi, Genes, Gram-Positive Bacteria, Hemolymph, Humans, Insect, Insect Proteins, Membrane Glycoproteins, Micrococcus luteus, Mutation, Receptors, Sequence Homology, Toll-Like Receptors @article{michel_drosophila_2001, title = {Drosophila Toll is activated by Gram-positive bacteria through a circulating peptidoglycan recognition protein}, author = { T. Michel and Jean-Marc Reichhart and Jules A. Hoffmann and Julien Royet}, doi = {10.1038/414756a}, issn = {0028-0836}, year = {2001}, date = {2001-12-01}, journal = {Nature}, volume = {414}, number = {6865}, pages = {756--759}, abstract = {Microbial infection activates two distinct intracellular signalling cascades in the immune-responsive fat body of Drosophila. Gram-positive bacteria and fungi predominantly induce the Toll signalling pathway, whereas Gram-negative bacteria activate the Imd pathway. Loss-of-function mutants in either pathway reduce the resistance to corresponding infections. Genetic screens have identified a range of genes involved in these intracellular signalling cascades, but how they are activated by microbial infection is largely unknown. Activation of the transmembrane receptor Toll requires a proteolytically cleaved form of an extracellular cytokine-like polypeptide, Spätzle, suggesting that Toll does not itself function as a bona fide recognition receptor of microbial patterns. This is in apparent contrast with the mammalian Toll-like receptors and raises the question of which host molecules actually recognize microbial patterns to activate Toll through Spätzle. Here we present a mutation that blocks Toll activation by Gram-positive bacteria and significantly decreases resistance to this type of infection. The mutation semmelweis (seml) inactivates the gene encoding a peptidoglycan recognition protein (PGRP-SA). Interestingly, seml does not affect Toll activation by fungal infection, indicating the existence of a distinct recognition system for fungi to activate the Toll pathway.}, keywords = {Amino Acid, Anti-Bacterial Agents, Anti-Infective Agents, Bacillus thuringiensis, Carrier Proteins, Cell Surface, Chromosome Mapping, Enterococcus faecalis, Fungi, Genes, Gram-Positive Bacteria, Hemolymph, Humans, Insect, Insect Proteins, Membrane Glycoproteins, Micrococcus luteus, Mutation, Receptors, Sequence Homology, Toll-Like Receptors}, pubstate = {published}, tppubtype = {article} } Microbial infection activates two distinct intracellular signalling cascades in the immune-responsive fat body of Drosophila. Gram-positive bacteria and fungi predominantly induce the Toll signalling pathway, whereas Gram-negative bacteria activate the Imd pathway. Loss-of-function mutants in either pathway reduce the resistance to corresponding infections. Genetic screens have identified a range of genes involved in these intracellular signalling cascades, but how they are activated by microbial infection is largely unknown. Activation of the transmembrane receptor Toll requires a proteolytically cleaved form of an extracellular cytokine-like polypeptide, Spätzle, suggesting that Toll does not itself function as a bona fide recognition receptor of microbial patterns. This is in apparent contrast with the mammalian Toll-like receptors and raises the question of which host molecules actually recognize microbial patterns to activate Toll through Spätzle. Here we present a mutation that blocks Toll activation by Gram-positive bacteria and significantly decreases resistance to this type of infection. The mutation semmelweis (seml) inactivates the gene encoding a peptidoglycan recognition protein (PGRP-SA). Interestingly, seml does not affect Toll activation by fungal infection, indicating the existence of a distinct recognition system for fungi to activate the Toll pathway. |
| 8. | Georgel, Philippe; Naitza, S; Kappler, Christine ; Ferrandon, Dominique ; Zachary, Daniel ; Swimmer, C; Kopczynski, C; Duyk, G; Reichhart, Jean-Marc ; Hoffmann, Jules A Drosophila immune deficiency (IMD) is a death domain protein that activates antibacterial defense and can promote apoptosis Article de journal Dev. Cell, 1 (4), p. 503–514, 2001, ISSN: 1534-5807. Résumé | BibTeX | Étiquettes: Anti-Infective Agents, Apoptosis, Bacterial Infections, Caspases, Chromosome Mapping, Cysteine Proteinase Inhibitors, DNA Damage, Female, Gene Expression, I-kappa B Kinase, Immunocompromised Host, In Situ Nick-End Labeling, Insect Proteins, Male, Mutation, Phenotype, Protein Structure, Protein-Serine-Threonine Kinases, Tertiary @article{georgel_drosophila_2001, title = {Drosophila immune deficiency (IMD) is a death domain protein that activates antibacterial defense and can promote apoptosis}, author = { Philippe Georgel and S. Naitza and Christine Kappler and Dominique Ferrandon and Daniel Zachary and C. Swimmer and C. Kopczynski and G. Duyk and Jean-Marc Reichhart and Jules A. Hoffmann}, issn = {1534-5807}, year = {2001}, date = {2001-10-01}, journal = {Dev. Cell}, volume = {1}, number = {4}, pages = {503--514}, abstract = {We report the molecular characterization of the immune deficiency (imd) gene, which controls antibacterial defense in Drosophila. imd encodes a protein with a death domain similar to that of mammalian RIP (receptor interacting protein), a protein that plays a role in both NF-kappaB activation and apoptosis. We show that imd functions upstream of the DmIKK signalosome and the caspase DREDD in the control of antibacterial peptide genes. Strikingly, overexpression of imd leads to constitutive transcription of these genes and to apoptosis, and both effects are blocked by coexpression of the caspase inhibitor P35. We also show that imd is involved in the apoptotic response to UV irradiation. These data raise the possibility that antibacterial response and apoptosis share common control elements in Drosophila.}, keywords = {Anti-Infective Agents, Apoptosis, Bacterial Infections, Caspases, Chromosome Mapping, Cysteine Proteinase Inhibitors, DNA Damage, Female, Gene Expression, I-kappa B Kinase, Immunocompromised Host, In Situ Nick-End Labeling, Insect Proteins, Male, Mutation, Phenotype, Protein Structure, Protein-Serine-Threonine Kinases, Tertiary}, pubstate = {published}, tppubtype = {article} } We report the molecular characterization of the immune deficiency (imd) gene, which controls antibacterial defense in Drosophila. imd encodes a protein with a death domain similar to that of mammalian RIP (receptor interacting protein), a protein that plays a role in both NF-kappaB activation and apoptosis. We show that imd functions upstream of the DmIKK signalosome and the caspase DREDD in the control of antibacterial peptide genes. Strikingly, overexpression of imd leads to constitutive transcription of these genes and to apoptosis, and both effects are blocked by coexpression of the caspase inhibitor P35. We also show that imd is involved in the apoptotic response to UV irradiation. These data raise the possibility that antibacterial response and apoptosis share common control elements in Drosophila. |
2000 |
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| 7. | Lagueux, Marie; Perrodou, E; Levashina, Elena A; Capovilla, Maria; Hoffmann, Jules A Constitutive expression of a complement-like protein in toll and JAK gain-of-function mutants of Drosophila Article de journal Proc. Natl. Acad. Sci. U.S.A., 97 (21), p. 11427–11432, 2000, ISSN: 0027-8424. Résumé | Liens | BibTeX | Étiquettes: alpha-Macroglobulins, Amino Acid, Cell Surface, Complement C3, Esters, Genetic, Insect Proteins, Janus Kinases, Membrane Glycoproteins, Mutation, Protein-Tyrosine Kinases, Proteins, Receptors, Sequence Homology, Sulfhydryl Compounds, Toll-Like Receptors, Transcription, Transcription Factors @article{lagueux_constitutive_2000, title = {Constitutive expression of a complement-like protein in toll and JAK gain-of-function mutants of Drosophila}, author = { Marie Lagueux and E. Perrodou and Elena A. Levashina and Maria Capovilla and Jules A. Hoffmann}, doi = {10.1073/pnas.97.21.11427}, issn = {0027-8424}, year = {2000}, date = {2000-10-01}, journal = {Proc. Natl. Acad. Sci. U.S.A.}, volume = {97}, number = {21}, pages = {11427--11432}, abstract = {We show that Drosophila expresses four genes encoding proteins with significant similarities with the thiolester-containing proteins of the complement C3/alpha(2)-macroglobulin superfamily. The genes are transcribed at a low level during all stages of development, and their expression is markedly up-regulated after an immune challenge. For one of these genes, which is predominantly expressed in the larval fat body, we observe a constitutive expression in gain-of-function mutants of the Janus kinase (JAK) hop and a reduced inducibility in loss-of-function hop mutants. We also observe a constitutive expression in gain-of-function Toll mutants. We discuss the possible roles of these novel complement-like proteins in the Drosophila host defense.}, keywords = {alpha-Macroglobulins, Amino Acid, Cell Surface, Complement C3, Esters, Genetic, Insect Proteins, Janus Kinases, Membrane Glycoproteins, Mutation, Protein-Tyrosine Kinases, Proteins, Receptors, Sequence Homology, Sulfhydryl Compounds, Toll-Like Receptors, Transcription, Transcription Factors}, pubstate = {published}, tppubtype = {article} } We show that Drosophila expresses four genes encoding proteins with significant similarities with the thiolester-containing proteins of the complement C3/alpha(2)-macroglobulin superfamily. The genes are transcribed at a low level during all stages of development, and their expression is markedly up-regulated after an immune challenge. For one of these genes, which is predominantly expressed in the larval fat body, we observe a constitutive expression in gain-of-function mutants of the Janus kinase (JAK) hop and a reduced inducibility in loss-of-function hop mutants. We also observe a constitutive expression in gain-of-function Toll mutants. We discuss the possible roles of these novel complement-like proteins in the Drosophila host defense. |
| 6. | Imler, Jean-Luc; Tauszig, Servane ; Jouanguy, Emmanuelle ; Forestier, C; Hoffmann, Jules A LPS-induced immune response in Drosophila Article de journal Journal of Endotoxin Research, 6 (6), p. 459–462, 2000, ISSN: 0968-0519. Résumé | BibTeX | Étiquettes: Biological, Cell Line, Cell Surface, Defensins, Genes, Genetic, Insect, Insect Proteins, Lipopolysaccharides, Membrane Glycoproteins, Models, Mutation, Promoter Regions, Receptors, Signal Transduction, Toll-Like Receptors @article{imler_lps-induced_2000, title = {LPS-induced immune response in Drosophila}, author = { Jean-Luc Imler and Servane Tauszig and Emmanuelle Jouanguy and C. Forestier and Jules A. Hoffmann}, issn = {0968-0519}, year = {2000}, date = {2000-01-01}, journal = {Journal of Endotoxin Research}, volume = {6}, number = {6}, pages = {459--462}, abstract = {The study of the regulation of the inducible synthesis of antimicrobial peptides in Drosophila melanogaster has established this insect as a powerful model in which to study innate immunity. In particular, the molecular characterization of the regulatory pathway controlling the antifungal peptide drosomycin has revealed the importance of Toll receptors in innate immunity. We report here that injection of LPS into flies induces an immune response, suggesting that LPS receptors are used in Drosophila to detect Gram-negative bacteria infection. We have identified in the recently sequenced genome of Drosophila eight genes coding for Toll-like receptors in addition to Toll, which may function as LPS receptors. However, overexpression of a selection of these genes in tissue-culture cells does not result in up-regulation of the antibacterial peptide genes. These results are discussed in light of the recent data from genetic screens aimed at identifying the genes controlling the antibacterial response in Drosophila.}, keywords = {Biological, Cell Line, Cell Surface, Defensins, Genes, Genetic, Insect, Insect Proteins, Lipopolysaccharides, Membrane Glycoproteins, Models, Mutation, Promoter Regions, Receptors, Signal Transduction, Toll-Like Receptors}, pubstate = {published}, tppubtype = {article} } The study of the regulation of the inducible synthesis of antimicrobial peptides in Drosophila melanogaster has established this insect as a powerful model in which to study innate immunity. In particular, the molecular characterization of the regulatory pathway controlling the antifungal peptide drosomycin has revealed the importance of Toll receptors in innate immunity. We report here that injection of LPS into flies induces an immune response, suggesting that LPS receptors are used in Drosophila to detect Gram-negative bacteria infection. We have identified in the recently sequenced genome of Drosophila eight genes coding for Toll-like receptors in addition to Toll, which may function as LPS receptors. However, overexpression of a selection of these genes in tissue-culture cells does not result in up-regulation of the antibacterial peptide genes. These results are discussed in light of the recent data from genetic screens aimed at identifying the genes controlling the antibacterial response in Drosophila. |
1999 |
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| 5. | Manfruelli, P; Reichhart, Jean-Marc ; Steward, R; Hoffmann, Jules A; Lemaitre, Bruno A mosaic analysis in Drosophila fat body cells of the control of antimicrobial peptide genes by the Rel proteins Dorsal and DIF Article de journal EMBO J., 18 (12), p. 3380–3391, 1999, ISSN: 0261-4189. Résumé | Liens | BibTeX | Étiquettes: Anti-Infective Agents, Cell Surface, Clone Cells, DNA-Binding Proteins, Fat Body, Female, Gene Expression Regulation, Genes, Insect, Insect Proteins, Larva, Male, Membrane Glycoproteins, Mosaicism, Mutation, Nuclear Proteins, Phosphoproteins, Receptors, Reporter, Signal Transduction, Toll-Like Receptors, Transcription Factors @article{manfruelli_mosaic_1999, title = {A mosaic analysis in Drosophila fat body cells of the control of antimicrobial peptide genes by the Rel proteins Dorsal and DIF}, author = { P. Manfruelli and Jean-Marc Reichhart and R. Steward and Jules A. Hoffmann and Bruno Lemaitre}, doi = {10.1093/emboj/18.12.3380}, issn = {0261-4189}, year = {1999}, date = {1999-06-01}, journal = {EMBO J.}, volume = {18}, number = {12}, pages = {3380--3391}, abstract = {Expression of the gene encoding the antifungal peptide Drosomycin in Drosophila adults is controlled by the Toll signaling pathway. The Rel proteins Dorsal and DIF (Dorsal-related immunity factor) are possible candidates for the transactivating protein in the Toll pathway that directly regulates the drosomycin gene. We have examined the requirement of Dorsal and DIF for drosomycin expression in larval fat body cells, the predominant immune-responsive tissue, using the yeast site-specific flp/FRT recombination system to generate cell clones homozygous for a deficiency uncovering both the dorsal and the dif genes. Here we show that in the absence of both genes, the immune-inducibility of drosomycin is lost but can be rescued by overexpression of either dorsal or dif under the control of a heat-shock promoter. This result suggests a functional redundancy between both Rel proteins in the control of drosomycin gene expression in the larvae of Drosophila. Interestingly, the gene encoding the antibacterial peptide Diptericin remains fully inducible in the absence of the dorsal and dif genes. Finally, we have used fat body cell clones homozygous for various mutations to show that a linear activation cascade Spaetzle--textgreater Toll--textgreaterCactus--textgreaterDorsal/DIF leads to the induction of the drosomycin gene in larval fat body cells.}, keywords = {Anti-Infective Agents, Cell Surface, Clone Cells, DNA-Binding Proteins, Fat Body, Female, Gene Expression Regulation, Genes, Insect, Insect Proteins, Larva, Male, Membrane Glycoproteins, Mosaicism, Mutation, Nuclear Proteins, Phosphoproteins, Receptors, Reporter, Signal Transduction, Toll-Like Receptors, Transcription Factors}, pubstate = {published}, tppubtype = {article} } Expression of the gene encoding the antifungal peptide Drosomycin in Drosophila adults is controlled by the Toll signaling pathway. The Rel proteins Dorsal and DIF (Dorsal-related immunity factor) are possible candidates for the transactivating protein in the Toll pathway that directly regulates the drosomycin gene. We have examined the requirement of Dorsal and DIF for drosomycin expression in larval fat body cells, the predominant immune-responsive tissue, using the yeast site-specific flp/FRT recombination system to generate cell clones homozygous for a deficiency uncovering both the dorsal and the dif genes. Here we show that in the absence of both genes, the immune-inducibility of drosomycin is lost but can be rescued by overexpression of either dorsal or dif under the control of a heat-shock promoter. This result suggests a functional redundancy between both Rel proteins in the control of drosomycin gene expression in the larvae of Drosophila. Interestingly, the gene encoding the antibacterial peptide Diptericin remains fully inducible in the absence of the dorsal and dif genes. Finally, we have used fat body cell clones homozygous for various mutations to show that a linear activation cascade Spaetzle--textgreater Toll--textgreaterCactus--textgreaterDorsal/DIF leads to the induction of the drosomycin gene in larval fat body cells. |
1998 |
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| 4. | Levashina, Elena A; Ohresser, S; Lemaitre, Bruno; Imler, Jean-Luc Two distinct pathways can control expression of the gene encoding the Drosophila antimicrobial peptide metchnikowin Article de journal Journal of Molecular Biology, 278 (3), p. 515–527, 1998, ISSN: 0022-2836. Résumé | Liens | BibTeX | Étiquettes: Anti-Infective Agents, Antimicrobial Cationic Peptides, Base Sequence, Cloning, Gene Expression Regulation, Genes, Genetic, Genetically Modified, Glycopeptides, Insect, Insect Proteins, Larva, Molecular, Mutation, Peptides, Promoter Regions, Recombinant Fusion Proteins, Reporter, Restriction Mapping, Transcription @article{levashina_two_1998, title = {Two distinct pathways can control expression of the gene encoding the Drosophila antimicrobial peptide metchnikowin}, author = { Elena A. Levashina and S. Ohresser and Bruno Lemaitre and Jean-Luc Imler}, doi = {10.1006/jmbi.1998.1705}, issn = {0022-2836}, year = {1998}, date = {1998-01-01}, journal = {Journal of Molecular Biology}, volume = {278}, number = {3}, pages = {515--527}, abstract = {Metchnikowin is a recently discovered proline-rich peptide from Drosophila with antibacterial and antifungal properties. Like most other antimicrobial peptides from insects, its expression is immune-inducible. Here we present evidence that induction of metchnikowin gene expression can be mediated either by the TOLL pathway or by the imd gene product. We show that the gene remains inducible in Toll-deficient mutants, in which the antifungal response is blocked, as well as in imd mutants, which fail to mount an antibacterial response. However, in Toll-deficient;imd double mutants, metchnikowin gene expression can no longer be detected after immune challenge. Our results suggest that expression of this peptide with dual activity can be triggered by signals generated by either bacterial or fungal infection. Cloning of the metchnikowin gene revealed the presence in the 5' flanking region of several putative cis-regulatory motifs characterized in the promoters of insect immune genes: namely, Rel sites, GATA motifs, interferon consensus response elements and NF-IL6 response elements. Establishment of transgenic fly lines in which the GFP reporter gene was placed under the control of 1.5 kb of metchnikowin gene upstream sequences indicates that this fragment is able to confer full immune inducibility and tissue specificity of expression on the transgene.}, keywords = {Anti-Infective Agents, Antimicrobial Cationic Peptides, Base Sequence, Cloning, Gene Expression Regulation, Genes, Genetic, Genetically Modified, Glycopeptides, Insect, Insect Proteins, Larva, Molecular, Mutation, Peptides, Promoter Regions, Recombinant Fusion Proteins, Reporter, Restriction Mapping, Transcription}, pubstate = {published}, tppubtype = {article} } Metchnikowin is a recently discovered proline-rich peptide from Drosophila with antibacterial and antifungal properties. Like most other antimicrobial peptides from insects, its expression is immune-inducible. Here we present evidence that induction of metchnikowin gene expression can be mediated either by the TOLL pathway or by the imd gene product. We show that the gene remains inducible in Toll-deficient mutants, in which the antifungal response is blocked, as well as in imd mutants, which fail to mount an antibacterial response. However, in Toll-deficient;imd double mutants, metchnikowin gene expression can no longer be detected after immune challenge. Our results suggest that expression of this peptide with dual activity can be triggered by signals generated by either bacterial or fungal infection. Cloning of the metchnikowin gene revealed the presence in the 5' flanking region of several putative cis-regulatory motifs characterized in the promoters of insect immune genes: namely, Rel sites, GATA motifs, interferon consensus response elements and NF-IL6 response elements. Establishment of transgenic fly lines in which the GFP reporter gene was placed under the control of 1.5 kb of metchnikowin gene upstream sequences indicates that this fragment is able to confer full immune inducibility and tissue specificity of expression on the transgene. |
1996 |
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Articles de journaux |
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| 3. | Lemaitre, Bruno; Nicolas, E; Michaut, Lydia ; Reichhart, Jean-Marc ; Hoffmann, Jules A The dorsoventral regulatory gene cassette spätzle/Toll/cactus controls the potent antifungal response in Drosophila adults Article de journal Cell, 86 (6), p. 973–983, 1996, ISSN: 0092-8674. Résumé | BibTeX | Étiquettes: Antifungal Agents, Cell Surface, DNA-Binding Proteins, Fungi, Gene Expression, Genes, Insect, Insect Hormones, Insect Proteins, Membrane Glycoproteins, MHC Class II, Mutation, Mycoses, NF-kappa B, Phosphoproteins, Proteins, Receptors, Signal Transduction, Toll-Like Receptors @article{lemaitre_dorsoventral_1996, title = {The dorsoventral regulatory gene cassette spätzle/Toll/cactus controls the potent antifungal response in Drosophila adults}, author = { Bruno Lemaitre and E. Nicolas and Lydia Michaut and Jean-Marc Reichhart and Jules A. Hoffmann}, issn = {0092-8674}, year = {1996}, date = {1996-01-01}, journal = {Cell}, volume = {86}, number = {6}, pages = {973--983}, abstract = {The cytokine-induced activation cascade of NF-kappaB in mammals and the activation of the morphogen dorsal in Drosophila embryos show striking structural and functional similarities (Toll/IL-1, Cactus/I-kappaB, and dorsal/NF-kappaB). Here we demonstrate that these parallels extend to the immune response of Drosophila. In particular, the intracellular components of the dorsoventral signaling pathway (except for dorsal) and the extracellular Toll ligand, spätzle, control expression of the antifungal peptide gene drosomycin in adults. We also show that mutations in the Toll signaling pathway dramatically reduce survival after fungal infection. Antibacterial genes are induced either by a distinct pathway involving the immune deficiency gene (imd) or by combined activation of both imd and dorsoventral pathways.}, keywords = {Antifungal Agents, Cell Surface, DNA-Binding Proteins, Fungi, Gene Expression, Genes, Insect, Insect Hormones, Insect Proteins, Membrane Glycoproteins, MHC Class II, Mutation, Mycoses, NF-kappa B, Phosphoproteins, Proteins, Receptors, Signal Transduction, Toll-Like Receptors}, pubstate = {published}, tppubtype = {article} } The cytokine-induced activation cascade of NF-kappaB in mammals and the activation of the morphogen dorsal in Drosophila embryos show striking structural and functional similarities (Toll/IL-1, Cactus/I-kappaB, and dorsal/NF-kappaB). Here we demonstrate that these parallels extend to the immune response of Drosophila. In particular, the intracellular components of the dorsoventral signaling pathway (except for dorsal) and the extracellular Toll ligand, spätzle, control expression of the antifungal peptide gene drosomycin in adults. We also show that mutations in the Toll signaling pathway dramatically reduce survival after fungal infection. Antibacterial genes are induced either by a distinct pathway involving the immune deficiency gene (imd) or by combined activation of both imd and dorsoventral pathways. |
1995 |
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Articles de journaux |
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| 2. | Lemaitre, Bruno; Kromer-Metzger, E; Michaut, Lydia ; Nicolas, E; Meister, Marie ; Georgel, Philippe ; Reichhart, Jean-Marc ; Hoffmann, Jules A A recessive mutation, immune deficiency (imd), defines two distinct control pathways in the Drosophila host defense Article de journal Proc. Natl. Acad. Sci. U.S.A., 92 (21), p. 9465–9469, 1995, ISSN: 0027-8424. Résumé | BibTeX | Étiquettes: Anti-Bacterial Agents, Antimicrobial Cationic Peptides, Bacterial Infections, Base Sequence, Gene Expression Regulation, Genes, Glycopeptides, Insect, Insect Hormones, Insect Proteins, Male, Mutation, Mycoses, Nucleic Acid, Peptides, Protein Binding, Recessive, Regulatory Sequences, Reporter, Survival Analysis @article{lemaitre_recessive_1995, title = {A recessive mutation, immune deficiency (imd), defines two distinct control pathways in the Drosophila host defense}, author = { Bruno Lemaitre and E. Kromer-Metzger and Lydia Michaut and E. Nicolas and Marie Meister and Philippe Georgel and Jean-Marc Reichhart and Jules A. Hoffmann}, issn = {0027-8424}, year = {1995}, date = {1995-10-01}, journal = {Proc. Natl. Acad. Sci. U.S.A.}, volume = {92}, number = {21}, pages = {9465--9469}, abstract = {In this paper we report a recessive mutation, immune deficiency (imd), that impairs the inducibility of all genes encoding antibacterial peptides during the immune response of Drosophila. When challenged with bacteria, flies carrying this mutation show a lower survival rate than wild-type flies. We also report that, in contrast to the antibacterial peptides, the antifungal peptide drosomycin remains inducible in a homozygous imd mutant background. These results point to the existence of two different pathways leading to the expression of two types of target genes, encoding either the antibacterial peptides or the antifungal peptide drosomycin.}, keywords = {Anti-Bacterial Agents, Antimicrobial Cationic Peptides, Bacterial Infections, Base Sequence, Gene Expression Regulation, Genes, Glycopeptides, Insect, Insect Hormones, Insect Proteins, Male, Mutation, Mycoses, Nucleic Acid, Peptides, Protein Binding, Recessive, Regulatory Sequences, Reporter, Survival Analysis}, pubstate = {published}, tppubtype = {article} } In this paper we report a recessive mutation, immune deficiency (imd), that impairs the inducibility of all genes encoding antibacterial peptides during the immune response of Drosophila. When challenged with bacteria, flies carrying this mutation show a lower survival rate than wild-type flies. We also report that, in contrast to the antibacterial peptides, the antifungal peptide drosomycin remains inducible in a homozygous imd mutant background. These results point to the existence of two different pathways leading to the expression of two types of target genes, encoding either the antibacterial peptides or the antifungal peptide drosomycin. |
| 1. | Lemaitre, Bruno; Meister, Marie ; Govind, S; Georgel, Philippe ; Steward, R; Reichhart, Jean-Marc ; Hoffmann, Jules A Functional analysis and regulation of nuclear import of dorsal during the immune response in Drosophila Article de journal EMBO J., 14 (3), p. 536–545, 1995, ISSN: 0261-4189. Résumé | BibTeX | Étiquettes: Anti-Bacterial Agents, Anti-Infective Agents, Antimicrobial Cationic Peptides, Biological Transport, Cell Nucleus, Cell Surface, DNA-Binding Proteins, Fat Body, Gene Expression Regulation, Genetic, Immunity, Immunohistochemistry, Insect Hormones, Insect Proteins, Melanins, Membrane Glycoproteins, Mutation, Neoplasms, Nuclear Proteins, Phosphoproteins, Receptors, Signal Transduction, Toll-Like Receptors, Transcription, Transcription Factors @article{lemaitre_functional_1995, title = {Functional analysis and regulation of nuclear import of dorsal during the immune response in Drosophila}, author = { Bruno Lemaitre and Marie Meister and S. Govind and Philippe Georgel and R. Steward and Jean-Marc Reichhart and Jules A. Hoffmann}, issn = {0261-4189}, year = {1995}, date = {1995-01-01}, journal = {EMBO J.}, volume = {14}, number = {3}, pages = {536--545}, abstract = {In addition to its function in embryonic development, the NF-kappa B/rel-related gene dorsal (dl) of Drosophila is expressed in larval and adult fat body where its RNA expression is enhanced upon injury. Injury also leads to a rapid nuclear translocation of dl from the cytoplasm in fat body cells. Here we present data which strongly suggest that the nuclear localization of dl during the immune response is controlled by the Toll signaling pathway, comprising gene products that participate in the intracellular part of the embryonic dorsoventral pathway. We also report that in mutants such as Toll or cactus, which exhibit melanotic tumor phenotypes, dl is constitutively nuclear. Together, these results point to a potential link between the Toll signaling pathway and melanotic tumor induction. Although dl has been shown previously to bind to kappa B-related motifs within the promoter of the antibacterial peptide coding gene diptericin, we find that injury-induced expression of diptericin can occur in the absence of dl. Furthermore, the melanotic tumor phenotype of Toll and cactus is not dl dependent. These data underline the complexity of the Drosophila immune response. Finally, we observed that like other rel proteins, dl can control the level of its own transcription.}, keywords = {Anti-Bacterial Agents, Anti-Infective Agents, Antimicrobial Cationic Peptides, Biological Transport, Cell Nucleus, Cell Surface, DNA-Binding Proteins, Fat Body, Gene Expression Regulation, Genetic, Immunity, Immunohistochemistry, Insect Hormones, Insect Proteins, Melanins, Membrane Glycoproteins, Mutation, Neoplasms, Nuclear Proteins, Phosphoproteins, Receptors, Signal Transduction, Toll-Like Receptors, Transcription, Transcription Factors}, pubstate = {published}, tppubtype = {article} } In addition to its function in embryonic development, the NF-kappa B/rel-related gene dorsal (dl) of Drosophila is expressed in larval and adult fat body where its RNA expression is enhanced upon injury. Injury also leads to a rapid nuclear translocation of dl from the cytoplasm in fat body cells. Here we present data which strongly suggest that the nuclear localization of dl during the immune response is controlled by the Toll signaling pathway, comprising gene products that participate in the intracellular part of the embryonic dorsoventral pathway. We also report that in mutants such as Toll or cactus, which exhibit melanotic tumor phenotypes, dl is constitutively nuclear. Together, these results point to a potential link between the Toll signaling pathway and melanotic tumor induction. Although dl has been shown previously to bind to kappa B-related motifs within the promoter of the antibacterial peptide coding gene diptericin, we find that injury-induced expression of diptericin can occur in the absence of dl. Furthermore, the melanotic tumor phenotype of Toll and cactus is not dl dependent. These data underline the complexity of the Drosophila immune response. Finally, we observed that like other rel proteins, dl can control the level of its own transcription. |
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