Publications
2014 |
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Articles de journaux |
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| 16. | 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. |
2012 |
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Articles de journaux |
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| 15. | Lemaitre, Bruno; Nicolas, Emmanuelle ; Michaut, Lydia ; Reichhart, Jean-Marc ; Hoffmann, Jules A Pillars article: the dorsoventral regulatory gene cassette spätzle/Toll/cactus controls the potent antifungal response in Drosophila adults. Cell. 1996. 86: 973-983 Article de journal J. Immunol., 188 (11), p. 5210–5220, 2012, ISSN: 1550-6606. Résumé | BibTeX | Étiquettes: Antifungal Agents, Developmental, DNA-Binding Proteins, Gene Expression Regulation, History, Multigene Family, Mycoses, Phosphoproteins, Toll-Like Receptors @article{lemaitre_pillars_2012, title = {Pillars article: the dorsoventral regulatory gene cassette spätzle/Toll/cactus controls the potent antifungal response in Drosophila adults. Cell. 1996. 86: 973-983}, author = { Bruno Lemaitre and Emmanuelle Nicolas and Lydia Michaut and Jean-Marc Reichhart and Jules A. Hoffmann}, issn = {1550-6606}, year = {2012}, date = {2012-06-01}, journal = {J. Immunol.}, volume = {188}, number = {11}, pages = {5210--5220}, 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 regulatory gene cassette, 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, Developmental, DNA-Binding Proteins, Gene Expression Regulation, History, Multigene Family, Mycoses, Phosphoproteins, 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 regulatory gene cassette, 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. |
2008 |
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Articles de journaux |
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| 14. | Roetzer, Andreas; Gregori, Christa; Jennings, Ann Marie; Quintin, Jessica; Ferrandon, Dominique; Butler, Geraldine; Kuchler, Karl; Ammerer, Gustav; Schüller, Christoph Candida glabrata environmental stress response involves Saccharomyces cerevisiae Msn2/4 orthologous transcription factors Article de journal Mol. Microbiol., 69 (3), p. 603–620, 2008, ISSN: 1365-2958. Résumé | Liens | BibTeX | Étiquettes: Candida glabrata, Candidiasis, DNA-Binding Proteins, Fungal, Fungal Proteins, Gene Expression Profiling, Gene Expression Regulation, Genetic, Humans, Oligonucleotide Array Sequence Analysis, Osmotic Pressure, Regulon, Saccharomyces cerevisiae Proteins, Transcription, Transcription Factors, Virulence, Yeasts @article{roetzer_candida_2008b, title = {Candida glabrata environmental stress response involves Saccharomyces cerevisiae Msn2/4 orthologous transcription factors}, author = { Andreas Roetzer and Christa Gregori and Ann Marie Jennings and Jessica Quintin and Dominique Ferrandon and Geraldine Butler and Karl Kuchler and Gustav Ammerer and Christoph Schüller}, doi = {10.1111/j.1365-2958.2008.06301.x}, issn = {1365-2958}, year = {2008}, date = {2008-01-01}, journal = {Mol. Microbiol.}, volume = {69}, number = {3}, pages = {603--620}, abstract = {We determined the genome-wide environmental stress response (ESR) expression profile of Candida glabrata, a human pathogen related to Saccharomyces cerevisiae. Despite different habitats, C. glabrata, S. cerevisiae, Schizosaccharomyces pombe and Candida albicans have a qualitatively similar ESR. We investigate the function of the C. glabrata syntenic orthologues to the ESR transcription factor Msn2. The C. glabrata orthologues CgMsn2 and CgMsn4 contain a motif previously referred to as HD1 (homology domain 1) also present in Msn2 orthologues from fungi closely related to S. cerevisiae. We show that regions including this motif confer stress-regulated intracellular localization when expressed in S. cerevisiae. Site-directed mutagenesis confirms that nuclear export of CgMsn2 in C. glabrata requires an intact HD1. Transcript profiles of CgMsn2/4 mutants and CgMsn2 overexpression strains show that they regulate a part of the CgESR. CgMsn2 complements a S. cerevisiae msn2 null mutant and in stressed C. glabrata cells, rapidly translocates from the cytosol to the nucleus. CgMsn2 is required for full resistance against severe osmotic stress and rapid and full induction of trehalose synthesis genes (TPS1, TPS2). Constitutive activation of CgMsn2 is detrimental for C. glabrata. These results establish an Msn2-regulated general stress response in C. glabrata.}, keywords = {Candida glabrata, Candidiasis, DNA-Binding Proteins, Fungal, Fungal Proteins, Gene Expression Profiling, Gene Expression Regulation, Genetic, Humans, Oligonucleotide Array Sequence Analysis, Osmotic Pressure, Regulon, Saccharomyces cerevisiae Proteins, Transcription, Transcription Factors, Virulence, Yeasts}, pubstate = {published}, tppubtype = {article} } We determined the genome-wide environmental stress response (ESR) expression profile of Candida glabrata, a human pathogen related to Saccharomyces cerevisiae. Despite different habitats, C. glabrata, S. cerevisiae, Schizosaccharomyces pombe and Candida albicans have a qualitatively similar ESR. We investigate the function of the C. glabrata syntenic orthologues to the ESR transcription factor Msn2. The C. glabrata orthologues CgMsn2 and CgMsn4 contain a motif previously referred to as HD1 (homology domain 1) also present in Msn2 orthologues from fungi closely related to S. cerevisiae. We show that regions including this motif confer stress-regulated intracellular localization when expressed in S. cerevisiae. Site-directed mutagenesis confirms that nuclear export of CgMsn2 in C. glabrata requires an intact HD1. Transcript profiles of CgMsn2/4 mutants and CgMsn2 overexpression strains show that they regulate a part of the CgESR. CgMsn2 complements a S. cerevisiae msn2 null mutant and in stressed C. glabrata cells, rapidly translocates from the cytosol to the nucleus. CgMsn2 is required for full resistance against severe osmotic stress and rapid and full induction of trehalose synthesis genes (TPS1, TPS2). Constitutive activation of CgMsn2 is detrimental for C. glabrata. These results establish an Msn2-regulated general stress response in C. glabrata. |
2006 |
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Articles de journaux |
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| 13. | 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. |
2005 |
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Articles de journaux |
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| 12. | 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: bioinformatic, DNA-Binding Proteins, Genetic, Genetically Modified, Insect Viruses, Janus Kinase 1, 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 = {bioinformatic, DNA-Binding Proteins, Genetic, Genetically Modified, Insect Viruses, Janus Kinase 1, 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. |
2002 |
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Articles de journaux |
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| 11. | Reichhart, Jean-Marc; Ligoxygakis, Petros ; Naitza, Silvia ; Woerfel, Gertrud ; Imler, Jean-Luc ; Gubb, David Splice-activated UAS hairpin vector gives complete RNAi knockout of single or double target transcripts in Drosophila melanogaster Article de journal Genesis (New York, N.Y.: 2000), 34 (1-2), p. 160–164, 2002, ISSN: 1526-954X. Liens | BibTeX | Étiquettes: DNA Transposable Elements, DNA-Binding Proteins, Enhancer Elements, Genetic, Genetic Vectors, Genetically Modified, Saccharomyces cerevisiae Proteins, Transcription Factors @article{reichhart_splice-activated_2002, title = {Splice-activated UAS hairpin vector gives complete RNAi knockout of single or double target transcripts in Drosophila melanogaster}, author = { Jean-Marc Reichhart and Petros Ligoxygakis and Silvia Naitza and Gertrud Woerfel and Jean-Luc Imler and David Gubb}, doi = {10.1002/gene.10122}, issn = {1526-954X}, year = {2002}, date = {2002-01-01}, journal = {Genesis (New York, N.Y.: 2000)}, volume = {34}, number = {1-2}, pages = {160--164}, keywords = {DNA Transposable Elements, DNA-Binding Proteins, Enhancer Elements, Genetic, Genetic Vectors, Genetically Modified, Saccharomyces cerevisiae Proteins, Transcription Factors}, pubstate = {published}, tppubtype = {article} } |
2000 |
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Articles de journaux |
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| 10. | Rutschmann, Sophie; Jung, Alain C; Hetru, Charles; Reichhart, Jean-Marc; Hoffmann, Jules A; Ferrandon, Dominique The Rel protein DIF mediates the antifungal but not the antibacterial host defense in Drosophila Article de journal Immunity, 12 (5), p. 569–580, 2000, ISSN: 1074-7613. Résumé | BibTeX | Étiquettes: Antigens, Bacterial, DNA-Binding Proteins, Fungal, Immunity, Innate, Transcription Factors @article{rutschmann_rel_2000, title = {The Rel protein DIF mediates the antifungal but not the antibacterial host defense in Drosophila}, author = {Sophie Rutschmann and Alain C. Jung and Charles Hetru and Jean-Marc Reichhart and Jules A. Hoffmann and Dominique Ferrandon}, issn = {1074-7613}, year = {2000}, date = {2000-05-01}, journal = {Immunity}, volume = {12}, number = {5}, pages = {569--580}, abstract = {We have isolated two Drosophila lines that carry point mutations in the gene coding for the NF-KB-like factor DIF. Like mutants of the Toll pathway, Dif mutant flies are susceptible to fungal but not to bacterial infections. Genetic epistasis experiments demonstrate that Dif mediates the Toll-dependent control of the inducibility of the antifungal peptide gene Drosomycin. Strikingly, DIF alone is required for the antifungal response in adults, but is redundant in larvae with Dorsal, another Rel family member. In Drosophila, Dif appears to be dedicated to the antifungal defense elicited by fungi and gram-positive bacteria. We discuss in this light the possibility that NF-KB1/p50 might be required more specifically in the innate immune response against gram-positive bacteria in mammals.}, keywords = {Antigens, Bacterial, DNA-Binding Proteins, Fungal, Immunity, Innate, Transcription Factors}, pubstate = {published}, tppubtype = {article} } We have isolated two Drosophila lines that carry point mutations in the gene coding for the NF-KB-like factor DIF. Like mutants of the Toll pathway, Dif mutant flies are susceptible to fungal but not to bacterial infections. Genetic epistasis experiments demonstrate that Dif mediates the Toll-dependent control of the inducibility of the antifungal peptide gene Drosomycin. Strikingly, DIF alone is required for the antifungal response in adults, but is redundant in larvae with Dorsal, another Rel family member. In Drosophila, Dif appears to be dedicated to the antifungal defense elicited by fungi and gram-positive bacteria. We discuss in this light the possibility that NF-KB1/p50 might be required more specifically in the innate immune response against gram-positive bacteria in mammals. |
| 9. | Imler, Jean-Luc; Hoffmann, Jules A Toll and Toll-like proteins: an ancient family of receptors signaling infection Article de journal Reviews in Immunogenetics, 2 (3), p. 294–304, 2000, ISSN: 1398-1714. Résumé | BibTeX | Étiquettes: Adaptor Proteins, Antigens, Autoantigens, CD14, Cell Adhesion Molecules, Cell Surface, Differentiation, DNA-Binding Proteins, Gene Expression Regulation, I-kappa B Proteins, Immunity, Immunologic, Infection, Innate, Insect Proteins, Interleukin-1 Receptor-Associated Kinases, Knockout, Larva, Lipopolysaccharides, Mammals, MAP Kinase Signaling System, Membrane Glycoproteins, Membrane Proteins, Mice, Multigene Family, Myeloid Differentiation Factor 88, NF-kappa B, Peptidoglycan, Phosphorylation, Post-Translational, Protein Kinases, Protein Processing, Protein Structure, Receptors, Recombinant Fusion Proteins, Signal Transducing, Signal Transduction, Teichoic Acids, Tertiary, Toll-Like Receptor 4, Toll-Like Receptor 5, Toll-Like Receptor 6, Toll-Like Receptor 9, Toll-Like Receptors, Ubiquitins @article{imler_toll_2000, title = {Toll and Toll-like proteins: an ancient family of receptors signaling infection}, author = { Jean-Luc Imler and Jules A. Hoffmann}, issn = {1398-1714}, year = {2000}, date = {2000-01-01}, journal = {Reviews in Immunogenetics}, volume = {2}, number = {3}, pages = {294--304}, abstract = {Innate immunity is the first-line host defense of multicellular organisms that rapidly operates to limit infection upon exposure to microbes. It involves intracellular signaling pathways in the fruit-fly Drosophila and in mammals that show striking similarities. Recent genetic and biochemical data have revealed, in particular, that proteins of the Toll family play a critical role in the immediate response to infection. We review here the recent developments on the structural and functional characterization of this evolutionary ancient and important family of proteins, which can function as cytokine receptors (Toll in Drosophila) or pattern recognition receptors (TLR4 in mammals) and activate similar, albeit non identical signal transduction pathways, in flies and mammals.}, keywords = {Adaptor Proteins, Antigens, Autoantigens, CD14, Cell Adhesion Molecules, Cell Surface, Differentiation, DNA-Binding Proteins, Gene Expression Regulation, I-kappa B Proteins, Immunity, Immunologic, Infection, Innate, Insect Proteins, Interleukin-1 Receptor-Associated Kinases, Knockout, Larva, Lipopolysaccharides, Mammals, MAP Kinase Signaling System, Membrane Glycoproteins, Membrane Proteins, Mice, Multigene Family, Myeloid Differentiation Factor 88, NF-kappa B, Peptidoglycan, Phosphorylation, Post-Translational, Protein Kinases, Protein Processing, Protein Structure, Receptors, Recombinant Fusion Proteins, Signal Transducing, Signal Transduction, Teichoic Acids, Tertiary, Toll-Like Receptor 4, Toll-Like Receptor 5, Toll-Like Receptor 6, Toll-Like Receptor 9, Toll-Like Receptors, Ubiquitins}, pubstate = {published}, tppubtype = {article} } Innate immunity is the first-line host defense of multicellular organisms that rapidly operates to limit infection upon exposure to microbes. It involves intracellular signaling pathways in the fruit-fly Drosophila and in mammals that show striking similarities. Recent genetic and biochemical data have revealed, in particular, that proteins of the Toll family play a critical role in the immediate response to infection. We review here the recent developments on the structural and functional characterization of this evolutionary ancient and important family of proteins, which can function as cytokine receptors (Toll in Drosophila) or pattern recognition receptors (TLR4 in mammals) and activate similar, albeit non identical signal transduction pathways, in flies and mammals. |
1999 |
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Articles de journaux |
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| 8. | 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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Articles de journaux |
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| 7. | Nicolas, E; Reichhart, Jean-Marc ; Hoffmann, Jules A; Lemaitre, Bruno In vivo regulation of the IkappaB homologue cactus during the immune response of Drosophila Article de journal J. Biol. Chem., 273 (17), p. 10463–10469, 1998, ISSN: 0021-9258. Résumé | BibTeX | Étiquettes: Cell Surface, DNA-Binding Proteins, Gene Expression Regulation, Insect Proteins, Larva, Membrane Glycoproteins, Phosphoproteins, Proto-Oncogene Proteins, Receptors, Signal Transduction, Toll-Like Receptors, Transcription Factor RelB, Transcription Factors @article{nicolas_vivo_1998, title = {In vivo regulation of the IkappaB homologue cactus during the immune response of Drosophila}, author = { E. Nicolas and Jean-Marc Reichhart and Jules A. Hoffmann and Bruno Lemaitre}, issn = {0021-9258}, year = {1998}, date = {1998-04-01}, journal = {J. Biol. Chem.}, volume = {273}, number = {17}, pages = {10463--10469}, abstract = {The dorsoventral regulatory gene pathway (spätzle/Toll/cactus) controls the expression of several antimicrobial genes during the immune response of Drosophila. This regulatory cascade shows striking similarities with the cytokine-induced activation cascade of NF-kappaB during the inflammatory response in mammals. Here, we have studied the regulation of the IkappaB homologue Cactus in the fat body during the immune response. We observe that the cactus gene is up-regulated in response to immune challenge. Interestingly, the expression of the cactus gene is controlled by the spätzle/Toll/cactus gene pathway, indicating that the cactus gene is autoregulated. We also show that two Cactus isoforms are expressed in the cytoplasm of fat body cells and that they are rapidly degraded and resynthesized after immune challenge. This degradation is also dependent on the Toll signaling pathway. Altogether, our results underline the striking similarities between the regulation of IkappaB and cactus during the immune response.}, keywords = {Cell Surface, DNA-Binding Proteins, Gene Expression Regulation, Insect Proteins, Larva, Membrane Glycoproteins, Phosphoproteins, Proto-Oncogene Proteins, Receptors, Signal Transduction, Toll-Like Receptors, Transcription Factor RelB, Transcription Factors}, pubstate = {published}, tppubtype = {article} } The dorsoventral regulatory gene pathway (spätzle/Toll/cactus) controls the expression of several antimicrobial genes during the immune response of Drosophila. This regulatory cascade shows striking similarities with the cytokine-induced activation cascade of NF-kappaB during the inflammatory response in mammals. Here, we have studied the regulation of the IkappaB homologue Cactus in the fat body during the immune response. We observe that the cactus gene is up-regulated in response to immune challenge. Interestingly, the expression of the cactus gene is controlled by the spätzle/Toll/cactus gene pathway, indicating that the cactus gene is autoregulated. We also show that two Cactus isoforms are expressed in the cytoplasm of fat body cells and that they are rapidly degraded and resynthesized after immune challenge. This degradation is also dependent on the Toll signaling pathway. Altogether, our results underline the striking similarities between the regulation of IkappaB and cactus during the immune response. |
1996 |
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Articles de journaux |
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| 6. | Barillas-Mury, Carolina; Charlesworth, A; Gross, I; Richman, A; Hoffmann, Jules A; Kafatos, Fotis C Immune factor Gambif1, a new rel family member from the human malaria vector, Anopheles gambiae Article de journal EMBO J., 15 (17), p. 4691–4701, 1996, ISSN: 0261-4189. Résumé | BibTeX | Étiquettes: Amino Acid, Anopheles, Base Sequence, Biological Transport, Cell Nucleus, Cells, Complementary, Cultured, DNA, DNA-Binding Proteins, Insect Proteins, Insect Vectors, NF-kappa B, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-rel, Sequence Homology, Trans-Activators, Transcriptional Activation @article{barillas-mury_immune_1996, title = {Immune factor Gambif1, a new rel family member from the human malaria vector, Anopheles gambiae}, author = { Carolina Barillas-Mury and A. Charlesworth and I. Gross and A. Richman and Jules A. Hoffmann and Fotis C. Kafatos}, issn = {0261-4189}, year = {1996}, date = {1996-09-01}, journal = {EMBO J.}, volume = {15}, number = {17}, pages = {4691--4701}, abstract = {A novel rel family member, Gambif1 (gambiae immune factor 1), has been cloned from the human malaria vector, Anopheles gambiae, and shown to be most similar to Drosophila Dorsal and Dif. Gambif1 protein is translocated to the nucleus in fat body cells in response to bacterial challenge, although the mRNA is present at low levels at all developmental stages and is not induced by infection. DNA binding activity to the kappaB-like sites in the A.gambiae Defensin and the Drosophila Diptericin and Cecropin promoters is also induced in larval nuclear extracts following infection. Gambif1 has the ability to bind to kappaB-like sites in vitro. Co-transfection assays in Drosophila mbn-2 cells show that Gambif1 can activate transcription by interacting with the Drosophila Diptericin regulatory elements, but is not functionally equivalent to Dorsal in this assay. Gambif1 protein translocation to the nucleus and the appearance of kappaB-like DNA binding activity can serve as molecular markers of activation of the immune system and open up the possibility of studying the role of defence reactions in determining mosquito susceptibility/refractoriness to malaria infection.}, keywords = {Amino Acid, Anopheles, Base Sequence, Biological Transport, Cell Nucleus, Cells, Complementary, Cultured, DNA, DNA-Binding Proteins, Insect Proteins, Insect Vectors, NF-kappa B, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-rel, Sequence Homology, Trans-Activators, Transcriptional Activation}, pubstate = {published}, tppubtype = {article} } A novel rel family member, Gambif1 (gambiae immune factor 1), has been cloned from the human malaria vector, Anopheles gambiae, and shown to be most similar to Drosophila Dorsal and Dif. Gambif1 protein is translocated to the nucleus in fat body cells in response to bacterial challenge, although the mRNA is present at low levels at all developmental stages and is not induced by infection. DNA binding activity to the kappaB-like sites in the A.gambiae Defensin and the Drosophila Diptericin and Cecropin promoters is also induced in larval nuclear extracts following infection. Gambif1 has the ability to bind to kappaB-like sites in vitro. Co-transfection assays in Drosophila mbn-2 cells show that Gambif1 can activate transcription by interacting with the Drosophila Diptericin regulatory elements, but is not functionally equivalent to Dorsal in this assay. Gambif1 protein translocation to the nucleus and the appearance of kappaB-like DNA binding activity can serve as molecular markers of activation of the immune system and open up the possibility of studying the role of defence reactions in determining mosquito susceptibility/refractoriness to malaria infection. |
| 5. | Gross, I; Georgel, Philippe ; Kappler, Christine ; Reichhart, Jean-Marc ; Hoffmann, Jules A Drosophila immunity: a comparative analysis of the Rel proteins dorsal and Dif in the induction of the genes encoding diptericin and cecropin Article de journal Nucleic Acids Res., 24 (7), p. 1238–1245, 1996, ISSN: 0305-1048. Résumé | BibTeX | Étiquettes: Antimicrobial Cationic Peptides, Base Sequence, DNA Primers, DNA-Binding Proteins, Gene Expression Regulation, Genetic, Insect Hormones, Insect Proteins, NF-kappa B, Nuclear Proteins, Peptides, Phosphoproteins, Transcription, Transcription Factors, Transcriptional Activation @article{gross_drosophila_1996, title = {Drosophila immunity: a comparative analysis of the Rel proteins dorsal and Dif in the induction of the genes encoding diptericin and cecropin}, author = { I. Gross and Philippe Georgel and Christine Kappler and Jean-Marc Reichhart and Jules A. Hoffmann}, issn = {0305-1048}, year = {1996}, date = {1996-04-01}, journal = {Nucleic Acids Res.}, volume = {24}, number = {7}, pages = {1238--1245}, abstract = {In Drosophila, bacterial challenge induces the rapid transcription of several genes encoding potent antibacterial peptides. The upstream sequences of the diptericin and cecropin Al genes, which have been investigated in detail, contain two, respectively one sequence element homologous to the binding site of the mammalian nuclear factor kappaB. These elements have been shown to be mandatory for immune-induced transcription of both genes. Functional studies have shown that these kappaB-related elements can be the target for the Drosophila Rel proteins dorsal and Dif. Here we present a comparative analysis of the transactivating capacities of these proteins on reporter genes fused to either the diptericin or the cecropin kappaB-related motifs. We conclude from our results: (i) the kappaB motifs of the diptericin and cecropin genes are not functionally equivalent; (ii) the dorsal and Dif proteins have distinct DNA-binding characteristics; (iii) dorsal and Dif can heterodimerize in vitro; (iv) mutants containing no copies of dorsal and a single copy of Dif retain their full capacity to express the diptericin and cecropin genes in response to challenge.}, keywords = {Antimicrobial Cationic Peptides, Base Sequence, DNA Primers, DNA-Binding Proteins, Gene Expression Regulation, Genetic, Insect Hormones, Insect Proteins, NF-kappa B, Nuclear Proteins, Peptides, Phosphoproteins, Transcription, Transcription Factors, Transcriptional Activation}, pubstate = {published}, tppubtype = {article} } In Drosophila, bacterial challenge induces the rapid transcription of several genes encoding potent antibacterial peptides. The upstream sequences of the diptericin and cecropin Al genes, which have been investigated in detail, contain two, respectively one sequence element homologous to the binding site of the mammalian nuclear factor kappaB. These elements have been shown to be mandatory for immune-induced transcription of both genes. Functional studies have shown that these kappaB-related elements can be the target for the Drosophila Rel proteins dorsal and Dif. Here we present a comparative analysis of the transactivating capacities of these proteins on reporter genes fused to either the diptericin or the cecropin kappaB-related motifs. We conclude from our results: (i) the kappaB motifs of the diptericin and cecropin genes are not functionally equivalent; (ii) the dorsal and Dif proteins have distinct DNA-binding characteristics; (iii) dorsal and Dif can heterodimerize in vitro; (iv) mutants containing no copies of dorsal and a single copy of Dif retain their full capacity to express the diptericin and cecropin genes in response to challenge. |
| 4. | 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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| 3. | Georgel, Philippe; Kappler, Christine ; Langley, E; Gross, I; Nicolas, E; Reichhart, Jean-Marc ; Hoffmann, Jules A Drosophila immunity. A sequence homologous to mammalian interferon consensus response element enhances the activity of the diptericin promoter Article de journal Nucleic Acids Res., 23 (7), p. 1140–1145, 1995, ISSN: 0305-1048. Résumé | BibTeX | Étiquettes: Base Sequence, CCAAT-Enhancer-Binding Proteins, DNA, DNA-Binding Proteins, Genes, Genetic, Immunity, Insect, Insect Hormones, Insect Proteins, Interferons, Lipopolysaccharides, NF-kappa B, Nuclear Proteins, Plasmids, Promoter Regions, Up-Regulation @article{georgel_drosophila_1995, title = {Drosophila immunity. A sequence homologous to mammalian interferon consensus response element enhances the activity of the diptericin promoter}, author = { Philippe Georgel and Christine Kappler and E. Langley and I. Gross and E. Nicolas and Jean-Marc Reichhart and Jules A. Hoffmann}, issn = {0305-1048}, year = {1995}, date = {1995-04-01}, journal = {Nucleic Acids Res.}, volume = {23}, number = {7}, pages = {1140--1145}, abstract = {Bacterial challenge of larvae or adults of Drosophila induces the rapid transcription of several genes encoding antibacterial peptides with a large spectrum of activity. One of these peptides, the 82-residue anti-gram negative diptericin, is encoded by a single intronless gene and we are investigating the control of expression of this gene. Previous studies using both transgenic experiments and footprint analysis have highlighted the role in the induction of this gene of a 30 nucleotide region which contains three partially overlapping motifs with sequence homology to mammalian NF-kappa B and NF-IL6 response elements and to the GAAANN sequence present in the interferon consensus response elements of some mammalian interferon-induced genes. We now show that the latter sequence binds in immune responsive tissues (fat body, blood cells) of Drosophila a approximately 45 kDa polypeptide which cross-reacts with a polyserum directed against mammalian interferon Regulatory Factor-I. Using a transfection assay of Drosophila tumorous blood cells, we show that the GAAANN sequence positively regulates the activity of the diptericin promoter. We propose that this motif cooperatively interacts with the other response elements in the regulation of the diptericin gene expression.}, keywords = {Base Sequence, CCAAT-Enhancer-Binding Proteins, DNA, DNA-Binding Proteins, Genes, Genetic, Immunity, Insect, Insect Hormones, Insect Proteins, Interferons, Lipopolysaccharides, NF-kappa B, Nuclear Proteins, Plasmids, Promoter Regions, Up-Regulation}, pubstate = {published}, tppubtype = {article} } Bacterial challenge of larvae or adults of Drosophila induces the rapid transcription of several genes encoding antibacterial peptides with a large spectrum of activity. One of these peptides, the 82-residue anti-gram negative diptericin, is encoded by a single intronless gene and we are investigating the control of expression of this gene. Previous studies using both transgenic experiments and footprint analysis have highlighted the role in the induction of this gene of a 30 nucleotide region which contains three partially overlapping motifs with sequence homology to mammalian NF-kappa B and NF-IL6 response elements and to the GAAANN sequence present in the interferon consensus response elements of some mammalian interferon-induced genes. We now show that the latter sequence binds in immune responsive tissues (fat body, blood cells) of Drosophila a approximately 45 kDa polypeptide which cross-reacts with a polyserum directed against mammalian interferon Regulatory Factor-I. Using a transfection assay of Drosophila tumorous blood cells, we show that the GAAANN sequence positively regulates the activity of the diptericin promoter. We propose that this motif cooperatively interacts with the other response elements in the regulation of the diptericin gene expression. |
| 2. | 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. |
1993 |
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Articles de journaux |
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| 1. | Georgel, Philippe; Meister, Marie ; Kappler, Christine ; Lemaitre, Bruno ; Reichhart, Jean-Marc ; Hoffmann, Jules A Insect immunity: the diptericin promoter contains multiple functional regulatory sequences homologous to mammalian acute-phase response elements Article de journal Biochem. Biophys. Res. Commun., 197 (2), p. 508–517, 1993, ISSN: 0006-291X. Résumé | Liens | BibTeX | Étiquettes: Acute-Phase Proteins, Anti-Infective Agents, Base Sequence, Cell Line, Deoxyribonuclease I, DNA-Binding Proteins, Genetic, Insect Hormones, Insect Proteins, Larva, Mammals, NF-kappa B, Nucleic Acid, Oligonucleotide Probes, Polymerase Chain Reaction, Promoter Regions, Regulatory Sequences @article{georgel_insect_1993, title = {Insect immunity: the diptericin promoter contains multiple functional regulatory sequences homologous to mammalian acute-phase response elements}, author = { Philippe Georgel and Marie Meister and Christine Kappler and Bruno Lemaitre and Jean-Marc Reichhart and Jules A. Hoffmann}, doi = {10.1006/bbrc.1993.2508}, issn = {0006-291X}, year = {1993}, date = {1993-12-01}, journal = {Biochem. Biophys. Res. Commun.}, volume = {197}, number = {2}, pages = {508--517}, abstract = {We are using the diptericin gene as a model system to study the control of expression of the genes encoding antibacterial peptides during the Drosophila immune reaction. In order to investigate the putative regulatory regions in the diptericin promoter, we performed DNaseI footprinting experiments combined with gel-shift assays in two inducible systems: the larval fat body and a tumorous Drosophila blood cell line. Our results confirm the importance of kappa B-like elements previously described in the immune response of insects and reveal for the first time the involvement of other regions containing sequences homologous to mammalian acute-phase response elements.}, keywords = {Acute-Phase Proteins, Anti-Infective Agents, Base Sequence, Cell Line, Deoxyribonuclease I, DNA-Binding Proteins, Genetic, Insect Hormones, Insect Proteins, Larva, Mammals, NF-kappa B, Nucleic Acid, Oligonucleotide Probes, Polymerase Chain Reaction, Promoter Regions, Regulatory Sequences}, pubstate = {published}, tppubtype = {article} } We are using the diptericin gene as a model system to study the control of expression of the genes encoding antibacterial peptides during the Drosophila immune reaction. In order to investigate the putative regulatory regions in the diptericin promoter, we performed DNaseI footprinting experiments combined with gel-shift assays in two inducible systems: the larval fat body and a tumorous Drosophila blood cell line. Our results confirm the importance of kappa B-like elements previously described in the immune response of insects and reveal for the first time the involvement of other regions containing sequences homologous to mammalian acute-phase response elements. |
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