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2021
Andre C, Veillard F, Wolff P, Lobstein A M, Compain G, Monsarrat C, Reichhart J M, Burnouf D Y, Guichard G, Wagner J E
Antibacterial activity of a dual peptide targeting the Escherichia coli sliding clamp and the ribosome Article de journal
Dans: RSC Chem Biol, vol. 2, no. 4, p. 1296, 2021, ISBN: 34459830, (2633-0679 (Electronic) 2633-0679 (Linking) Published Erratum).
Résumé | Liens | BibTeX | Étiquettes: ARN-MS, ENNIFAR, reichhart, Unité ARN
@article{,
title = {Antibacterial activity of a dual peptide targeting the Escherichia coli sliding clamp and the ribosome},
author = {C Andre and F Veillard and P Wolff and A M Lobstein and G Compain and C Monsarrat and J M Reichhart and D Y Burnouf and G Guichard and J E Wagner},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=34459830},
doi = {10.1039/d1cb90020j},
isbn = {34459830},
year = {2021},
date = {2021-01-01},
journal = {RSC Chem Biol},
volume = {2},
number = {4},
pages = {1296},
abstract = {[This corrects the article DOI: 10.1039/D0CB00060D.].},
note = {2633-0679 (Electronic)
2633-0679 (Linking)
Published Erratum},
keywords = {ARN-MS, ENNIFAR, reichhart, Unité ARN},
pubstate = {published},
tppubtype = {article}
}
[This corrects the article DOI: 10.1039/D0CB00060D.].
2020
André Christophe, Veillard Florian, Wolff Philippe, Lobstein Anne-marie, Compain Guillaume, Monsarrat Clément, Reichhart Jean-marc, Noûs Camille, Burnouf Dominique, Guichard Gilles, Wagner Jerome
Antibacterial activity of a dual peptide targeting the Escherichia coli sliding clamp and the ribosome Article de journal
Dans: RSC Chemical Biology, vol. 1, no. 3, p. 137-147, 2020.
Résumé | Liens | BibTeX | Étiquettes: Antibacterial, Antimicrobial peptides, Bacterial, clamp, E. coli, M3i, reichhart
@article{veillard2020,
title = {Antibacterial activity of a dual peptide targeting the Escherichia coli sliding clamp and the ribosome},
author = {Christophe André and Florian Veillard and Philippe Wolff and Anne-marie Lobstein and Guillaume Compain and Clément Monsarrat and Jean-marc Reichhart and Camille Noûs and Dominique Burnouf and Gilles Guichard and Jerome Wagner },
url = {https://pubs.rsc.org/en/content/articlelanding/2020/CB/D0CB00060D#!divAbstract},
doi = {10.1039/D0CB00060D},
year = {2020},
date = {2020-07-16},
journal = {RSC Chemical Biology},
volume = {1},
number = {3},
pages = {137-147},
abstract = {The bacterial processivity factor, or sliding clamp (SC), is a target of choice for new antibacterial drugs development. We have previously developed peptides that target Escherichia coli SC and block its interaction with DNA polymerases in vitro. Here, one such SC binding peptide was fused to a Proline-rich AntiMicrobial Peptide (PrAMP) to allow its internalization into E. coli cells. Co-immunoprecipitation assays with a N-terminally modified bifunctional peptide that still enters the bacteria but fails to interact with the bacterial ribosome, the major target of PrAMPs, demonstrate that it actually interacts with the bacterial SC. Moreover, when compared to SC non-binding controls, this peptide induces a ten-fold higher antibacterial activity against E. coli, showing that the observed antimicrobial activity is linked to SC binding. Finally, an unmodified bifunctional compound significantly increases the survival of Drosophila melanogaster flies challenged by an E. coli infection. Our study demonstrates the potential of PrAMPs to transport antibiotics into the bacterial cytoplasm and validates the development of drugs targeting the bacterial processivity factor of Gram-negative bacteria as a promising new class of antibiotics.},
keywords = {Antibacterial, Antimicrobial peptides, Bacterial, clamp, E. coli, M3i, reichhart},
pubstate = {published},
tppubtype = {article}
}
The bacterial processivity factor, or sliding clamp (SC), is a target of choice for new antibacterial drugs development. We have previously developed peptides that target Escherichia coli SC and block its interaction with DNA polymerases in vitro. Here, one such SC binding peptide was fused to a Proline-rich AntiMicrobial Peptide (PrAMP) to allow its internalization into E. coli cells. Co-immunoprecipitation assays with a N-terminally modified bifunctional peptide that still enters the bacteria but fails to interact with the bacterial ribosome, the major target of PrAMPs, demonstrate that it actually interacts with the bacterial SC. Moreover, when compared to SC non-binding controls, this peptide induces a ten-fold higher antibacterial activity against E. coli, showing that the observed antimicrobial activity is linked to SC binding. Finally, an unmodified bifunctional compound significantly increases the survival of Drosophila melanogaster flies challenged by an E. coli infection. Our study demonstrates the potential of PrAMPs to transport antibiotics into the bacterial cytoplasm and validates the development of drugs targeting the bacterial processivity factor of Gram-negative bacteria as a promising new class of antibiotics.
2018
Issa Najwa, Guillaumot Nina, Lauret Emilie, Matt Nicolas, Scaeffer-Reiss Christine, Dorsselaer Alain Van, Reichhart Jean-Marc, Veillard Florian
The circulating protease Persephone is an immune sensor for microbial proteolytic activities upstream of the Drosophila Toll pathway. Article de journal
Dans: Molecular Cell, vol. 69, no. 4, p. 539-550, 2018, ISSN: 1097-2765.
Résumé | Liens | BibTeX | Étiquettes: circulating protease, immune sensor, M3i, matt, persephone, Protease, proteolitic activities, reichhart, toll pathway
@article{Issa2018,
title = {The circulating protease Persephone is an immune sensor for microbial proteolytic activities upstream of the Drosophila Toll pathway.},
author = {Najwa Issa and Nina Guillaumot and Emilie Lauret and Nicolas Matt and Christine Scaeffer-Reiss and Alain Van Dorsselaer and Jean-Marc Reichhart and Florian Veillard},
url = {http://www.cell.com/molecular-cell/fulltext/S1097-2765(18)30058-3?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1097276518300583%3Fshowall%3Dtrue},
doi = {10.1016/j.molcel.2018.01.029},
issn = {1097-2765},
year = {2018},
date = {2018-02-15},
journal = {Molecular Cell},
volume = {69},
number = {4},
pages = {539-550},
abstract = {Microbial or endogenous molecular patterns as well as pathogen functional features can activate innate immune systems. Whereas detection of infection by pattern recognition receptors has been investigated in details, sensing of virulence factors activities remains less characterized. In Drosophila, genetic evidences indicate that the serine protease Persephone belongs to a danger pathway activated by abnormal proteolytic activities to induce Toll signaling. However, neither the activation mechanism of this pathway nor its specificity has been determined. Here, we identify a unique region in the pro-domain of Persephone that functions as bait for exogenous proteases independently of their origin, type, or specificity. Cleavage in this bait region constitutes the first step of a sequential activation and licenses the subsequent maturation of Persephone to the endogenous cysteine cathepsin 26-29-p. Our results establish Persephone itself as an immune receptor able to sense a broad range of microbes through virulence factor activities rather than molecular patterns.},
keywords = {circulating protease, immune sensor, M3i, matt, persephone, Protease, proteolitic activities, reichhart, toll pathway},
pubstate = {published},
tppubtype = {article}
}
Microbial or endogenous molecular patterns as well as pathogen functional features can activate innate immune systems. Whereas detection of infection by pattern recognition receptors has been investigated in details, sensing of virulence factors activities remains less characterized. In Drosophila, genetic evidences indicate that the serine protease Persephone belongs to a danger pathway activated by abnormal proteolytic activities to induce Toll signaling. However, neither the activation mechanism of this pathway nor its specificity has been determined. Here, we identify a unique region in the pro-domain of Persephone that functions as bait for exogenous proteases independently of their origin, type, or specificity. Cleavage in this bait region constitutes the first step of a sequential activation and licenses the subsequent maturation of Persephone to the endogenous cysteine cathepsin 26-29-p. Our results establish Persephone itself as an immune receptor able to sense a broad range of microbes through virulence factor activities rather than molecular patterns.
2017
Koltun Bella, Shackelford Eliza, Bonnay François, Matt Nicolas, Reichhart Jean-Marc, Orian Amir
The SUMO-targeted ubiquitin ligase, Dgrn, is essential for Drosophila innate immunity Article de journal
Dans: The International Journal of Developmental Biology, vol. 61, no. 3-4-5, p. 319–327, 2017, ISSN: 0214-6282.
Liens | BibTeX | Étiquettes: Dgrn, Drosophila, innate immunity, Ligase, M3i, matt, reichhart, SUMO, target, ubiquitin
@article{koltun_sumo-targeted_2017,
title = {The SUMO-targeted ubiquitin ligase, Dgrn, is essential for Drosophila innate immunity},
author = {Bella Koltun and Eliza Shackelford and François Bonnay and Nicolas Matt and Jean-Marc Reichhart and Amir Orian},
url = {http://www.intjdevbiol.com/paper.php?doi=160250ao},
doi = {10.1387/ijdb.160250ao},
issn = {0214-6282},
year = {2017},
date = {2017-01-01},
urldate = {2017-07-12},
journal = {The International Journal of Developmental Biology},
volume = {61},
number = {3-4-5},
pages = {319--327},
keywords = {Dgrn, Drosophila, innate immunity, Ligase, M3i, matt, reichhart, SUMO, target, ubiquitin},
pubstate = {published},
tppubtype = {article}
}
Chamy Laure El, Matt Nicolas, Reichhart Jean-Marc
Advances in Myeloid-Like Cell Origins and Functions in the Model Organism Drosophila melanogaster Article de journal
Dans: Microbiology Spectrum, vol. 5, no. 1, 2017, ISSN: 2165-0497.
Liens | BibTeX | Étiquettes: Drosophila melanogaster, M3i, matt, Myeloid-Like Cell Origins, reichhart
@article{Chamy2017,
title = {Advances in Myeloid-Like Cell Origins and Functions in the Model Organism Drosophila melanogaster},
author = {Laure El Chamy and Nicolas Matt and Jean-Marc Reichhart},
url = {http://www.asmscience.org/content/journal/microbiolspec/10.1128/microbiolspec.MCHD-0038-2016},
doi = {10.1128/microbiolspec.MCHD-0038-2016},
issn = {2165-0497},
year = {2017},
date = {2017-01-01},
urldate = {2017-07-12},
journal = {Microbiology Spectrum},
volume = {5},
number = {1},
keywords = {Drosophila melanogaster, M3i, matt, Myeloid-Like Cell Origins, reichhart},
pubstate = {published},
tppubtype = {article}
}
2016
Baron Olga Lucia, Deleury Emeline, Reichhart Jean-Marc, Coustau Christine
The LBP/BPI multigenic family in invertebrates: Evolutionary history and evidences of specialization in mollusks Article de journal
Dans: Developmental & Comparative Immunology, vol. 57, p. 20–30, 2016, ISSN: 0145305X.
Liens | BibTeX | Étiquettes: BPI, Evolution, Invertebrate, LBP, M3i, mollusks, multigenic family, reichhart
@article{baron_lbp/bpi_2016,
title = {The LBP/BPI multigenic family in invertebrates: Evolutionary history and evidences of specialization in mollusks},
author = {Olga Lucia Baron and Emeline Deleury and Jean-Marc Reichhart and Christine Coustau},
url = {http://linkinghub.elsevier.com/retrieve/pii/S0145305X15300756},
doi = {10.1016/j.dci.2015.11.006},
issn = {0145305X},
year = {2016},
date = {2016-01-01},
urldate = {2017-07-12},
journal = {Developmental & Comparative Immunology},
volume = {57},
pages = {20--30},
keywords = {BPI, Evolution, Invertebrate, LBP, M3i, mollusks, multigenic family, reichhart},
pubstate = {published},
tppubtype = {article}
}
2015
Veillard Florian, Troxler Laurent, Reichhart Jean-Marc
Drosophila melanogaster clip-domain serine proteases: Structure, function and regulation Article de journal
Dans: Biochimie, vol. 122, p. 255-269, 2015, ISBN: 0300-9084.
Résumé | Liens | BibTeX | Étiquettes: bioinformatic, Chymotrypsin, clip domain, Immunity, Insect, M3i, Melanization, reichhart, Serine Proteases, Serpin, Toll
@article{veillard_drosophila_2015,
title = {Drosophila melanogaster clip-domain serine proteases: Structure, function and regulation},
author = {Florian Veillard and Laurent Troxler and Jean-Marc Reichhart},
url = {http://www.sciencedirect.com/science/article/pii/S030090841500317X},
doi = {10.1016/j.biochi.2015.10.007},
isbn = {0300-9084},
year = {2015},
date = {2015-10-08},
journal = {Biochimie},
volume = {122},
pages = {255-269},
abstract = {Mammalian chymotrypsin-like serine proteases (SPs) are one of the best-studied family of enzymes with roles in a wide range of physiological processes, including digestion, blood coagulation, fibrinolysis and humoral immunity. Extracellular SPs can form cascades, in which one protease activates the zymogen of the next protease in the chain, to amplify physiological or pathological signals. These extracellular SPs are generally multi-domain proteins, with pro-domains that are involved in protein–protein interactions critical for the sequential organization of the cascades, the control of their intensity and their proper localization. Far less is known about invertebrate SPs than their mammalian counterparts. In insect genomes, SPs and their proteolytically inactive homologs (SPHs) constitute large protein families. In addition to the chymotrypsin fold, many of these proteins contain additional structural domains, often with conserved mammalian orthologues. However, the largest group of arthropod SP regulatory modules is the clip domains family, which has only been identified in arthropods. The clip-domain SPs are extracellular and have roles in the immune response and embryonic development. The powerful reverse-genetics tools in Drosophila melanogaster have been essential to identify the functions of clip-SPs and their organization in sequential cascades. This review focuses on the current knowledge of Drosophila clip-SPs and presents, when necessary, data obtained in other insect models. We will first cover the biochemical and structural features of clip domain SPs and SPHs. Clip-SPs are implicated in three main biological processes: the control of the dorso-ventral patterning during embryonic development; the activation of the Toll-mediated response to microbial infections and the prophenoloxydase cascade, which triggers melanization. Finally, we review the regulation of SPs and SPHs, from specificity of activation to inhibition by endogenous or pathogen-encoded inhibitors.},
keywords = {bioinformatic, Chymotrypsin, clip domain, Immunity, Insect, M3i, Melanization, reichhart, Serine Proteases, Serpin, Toll},
pubstate = {published},
tppubtype = {article}
}
Mammalian chymotrypsin-like serine proteases (SPs) are one of the best-studied family of enzymes with roles in a wide range of physiological processes, including digestion, blood coagulation, fibrinolysis and humoral immunity. Extracellular SPs can form cascades, in which one protease activates the zymogen of the next protease in the chain, to amplify physiological or pathological signals. These extracellular SPs are generally multi-domain proteins, with pro-domains that are involved in protein–protein interactions critical for the sequential organization of the cascades, the control of their intensity and their proper localization. Far less is known about invertebrate SPs than their mammalian counterparts. In insect genomes, SPs and their proteolytically inactive homologs (SPHs) constitute large protein families. In addition to the chymotrypsin fold, many of these proteins contain additional structural domains, often with conserved mammalian orthologues. However, the largest group of arthropod SP regulatory modules is the clip domains family, which has only been identified in arthropods. The clip-domain SPs are extracellular and have roles in the immune response and embryonic development. The powerful reverse-genetics tools in Drosophila melanogaster have been essential to identify the functions of clip-SPs and their organization in sequential cascades. This review focuses on the current knowledge of Drosophila clip-SPs and presents, when necessary, data obtained in other insect models. We will first cover the biochemical and structural features of clip domain SPs and SPHs. Clip-SPs are implicated in three main biological processes: the control of the dorso-ventral patterning during embryonic development; the activation of the Toll-mediated response to microbial infections and the prophenoloxydase cascade, which triggers melanization. Finally, we review the regulation of SPs and SPHs, from specificity of activation to inhibition by endogenous or pathogen-encoded inhibitors.
Chamy Laure El, Matt Nicolas, Ntwasa Monde, Reichhart Jean-Marc
The multilayered innate immune defense of the gut Article de journal
Dans: Biomed J, vol. 38, no. 4, p. 276–284, 2015, ISSN: 2320-2890.
Résumé | Liens | BibTeX | Étiquettes: fly, gut, innate immunity, M3i, matt, reichhart
@article{el_chamy_multilayered_2015,
title = {The multilayered innate immune defense of the gut},
author = {Laure El Chamy and Nicolas Matt and Monde Ntwasa and Jean-Marc Reichhart},
url = {http://www.biomedj.org/text.asp?2015/38/4/276/158621},
doi = {10.4103/2319-4170.158621},
issn = {2320-2890},
year = {2015},
date = {2015-08-01},
journal = {Biomed J},
volume = {38},
number = {4},
pages = {276--284},
abstract = {In the wild, the fruit fly Drosophila melanogaster thrives on rotten fruit. The digestive tract maintains a powerful gut immune barrier to regulate the ingested microbiota, including entomopathogenic bacteria. This gut immune barrier includes a chitinous peritrophic matrix that isolates the gut contents from the epithelial cells. In addition, the epithelial cells are tightly sealed by septate junctions and can mount an inducible immune response. This local response can be activated by invasive bacteria, or triggered by commensal bacteria in the gut lumen. As with chronic inflammation in mammals, constitutive activation of the gut innate immune response is detrimental to the health of flies. Accordingly, the Drosophila gut innate immune response is tightly regulated to maintain the endogenous microbiota, while preventing infections by pathogenic microorganisms.},
keywords = {fly, gut, innate immunity, M3i, matt, reichhart},
pubstate = {published},
tppubtype = {article}
}
In the wild, the fruit fly Drosophila melanogaster thrives on rotten fruit. The digestive tract maintains a powerful gut immune barrier to regulate the ingested microbiota, including entomopathogenic bacteria. This gut immune barrier includes a chitinous peritrophic matrix that isolates the gut contents from the epithelial cells. In addition, the epithelial cells are tightly sealed by septate junctions and can mount an inducible immune response. This local response can be activated by invasive bacteria, or triggered by commensal bacteria in the gut lumen. As with chronic inflammation in mammals, constitutive activation of the gut innate immune response is detrimental to the health of flies. Accordingly, the Drosophila gut innate immune response is tightly regulated to maintain the endogenous microbiota, while preventing infections by pathogenic microorganisms.
2014
Bonnay François, Nguyen Xuan-Hung, Cohen-Berros Eva, Troxler Laurent, Batsche Eric, Camonis Jacques, Takeuchi Osamu, Reichhart Jean-Marc, Matt Nicolas
Akirin specifies NF-κB selectivity of Drosophila innate immune response via chromatin remodeling Article de journal
Dans: EMBO J., vol. 33, no. 20, p. 2349–2362, 2014, ISSN: 1460-2075.
Résumé | Liens | BibTeX | Étiquettes: Animals, bioinformatic, Cell Cycle Proteins, Chromatin Assembly and Disassembly, chromatin remodeling, DNA-Binding Proteins, Female, Genetic, Immunity, Innate, Innate immune response, M3i, Male, matt, Mutation, NF-kappa B, NF‐κB, Promoter Regions, proteomics, reichhart, Trans-Activators, Transcription Factors, Transcriptional Activation, Two-Hybrid System Techniques
@article{bonnay_akirin_2014,
title = {Akirin specifies NF-κB selectivity of Drosophila innate immune response via chromatin remodeling},
author = {François Bonnay and Xuan-Hung Nguyen and Eva Cohen-Berros and Laurent Troxler and Eric Batsche and Jacques Camonis and Osamu Takeuchi and Jean-Marc Reichhart and Nicolas Matt},
doi = {10.15252/embj.201488456},
issn = {1460-2075},
year = {2014},
date = {2014-10-01},
journal = {EMBO J.},
volume = {33},
number = {20},
pages = {2349--2362},
abstract = {The network of NF-κB-dependent transcription that activates both pro- and anti-inflammatory genes in mammals is still unclear. As NF-κB factors are evolutionarily conserved, we used Drosophila to understand this network. The NF-κB transcription factor Relish activates effector gene expression following Gram-negative bacterial immune challenge. Here, we show, using a genome-wide approach, that the conserved nuclear protein Akirin is a NF-κB co-factor required for the activation of a subset of Relish-dependent genes correlating with the presence of H3K4ac epigenetic marks. A large-scale unbiased proteomic analysis revealed that Akirin orchestrates NF-κB transcriptional selectivity through the recruitment of the Osa-containing-SWI/SNF-like Brahma complex (BAP). Immune challenge in Drosophila shows that Akirin is required for the transcription of a subset of effector genes, but dispensable for the transcription of genes that are negative regulators of the innate immune response. Therefore, Akirins act as molecular selectors specifying the choice between subsets of NF-κB target genes. The discovery of this mechanism, conserved in mammals, paves the way for the establishment of more specific and less toxic anti-inflammatory drugs targeting pro-inflammatory genes.},
keywords = {Animals, bioinformatic, Cell Cycle Proteins, Chromatin Assembly and Disassembly, chromatin remodeling, DNA-Binding Proteins, Female, Genetic, Immunity, Innate, Innate immune response, M3i, Male, matt, Mutation, NF-kappa B, NF‐κB, Promoter Regions, proteomics, reichhart, Trans-Activators, Transcription Factors, Transcriptional Activation, Two-Hybrid System Techniques},
pubstate = {published},
tppubtype = {article}
}
The network of NF-κB-dependent transcription that activates both pro- and anti-inflammatory genes in mammals is still unclear. As NF-κB factors are evolutionarily conserved, we used Drosophila to understand this network. The NF-κB transcription factor Relish activates effector gene expression following Gram-negative bacterial immune challenge. Here, we show, using a genome-wide approach, that the conserved nuclear protein Akirin is a NF-κB co-factor required for the activation of a subset of Relish-dependent genes correlating with the presence of H3K4ac epigenetic marks. A large-scale unbiased proteomic analysis revealed that Akirin orchestrates NF-κB transcriptional selectivity through the recruitment of the Osa-containing-SWI/SNF-like Brahma complex (BAP). Immune challenge in Drosophila shows that Akirin is required for the transcription of a subset of effector genes, but dispensable for the transcription of genes that are negative regulators of the innate immune response. Therefore, Akirins act as molecular selectors specifying the choice between subsets of NF-κB target genes. The discovery of this mechanism, conserved in mammals, paves the way for the establishment of more specific and less toxic anti-inflammatory drugs targeting pro-inflammatory genes.
Tartey Sarang, Matsushita Kazufumi, Vandenbon Alexis, Ori Daisuke, Imamura Tomoko, Mino Takashi, Standley Daron M, Hoffmann Jules A, Reichhart Jean-Marc, Akira Shizuo, Takeuchi Osamu
Akirin2 is critical for inducing inflammatory genes by bridging IκB-ζ and the SWI/SNF complex Article de journal
Dans: EMBO J., vol. 33, no. 20, p. 2332–2348, 2014, ISSN: 1460-2075.
Résumé | Liens | BibTeX | Étiquettes: Adaptor Proteins, Animals, Cell Nucleus, Chromatin Assembly and Disassembly, chromatin remodeling, Chromosomal Proteins, cytokine, Cytokines, Female, Gene Expression Regulation, gene regulation, Genetic, hoffmann, Humans, Immunity, Innate, innate immunity, Knockout, Listeria monocytogenes, M3i, Macrophages, Male, Mice, Multiprotein Complexes, Non-Histone, Nuclear Proteins, Promoter Regions, Protein Binding, reichhart, Repressor Proteins, Sequence Deletion, Signal Transducing, Transcriptional Activation
@article{tartey_akirin2_2014,
title = {Akirin2 is critical for inducing inflammatory genes by bridging IκB-ζ and the SWI/SNF complex},
author = {Sarang Tartey and Kazufumi Matsushita and Alexis Vandenbon and Daisuke Ori and Tomoko Imamura and Takashi Mino and Daron M Standley and Jules A Hoffmann and Jean-Marc Reichhart and Shizuo Akira and Osamu Takeuchi},
doi = {10.15252/embj.201488447},
issn = {1460-2075},
year = {2014},
date = {2014-10-01},
journal = {EMBO J.},
volume = {33},
number = {20},
pages = {2332--2348},
abstract = {Transcription of inflammatory genes in innate immune cells is coordinately regulated by transcription factors, including NF-κB, and chromatin modifiers. However, it remains unclear how microbial sensing initiates chromatin remodeling. Here, we show that Akirin2, an evolutionarily conserved nuclear protein, bridges NF-κB and the chromatin remodeling SWI/SNF complex by interacting with BRG1-Associated Factor 60 (BAF60) proteins as well as IκB-ζ, which forms a complex with the NF-κB p50 subunit. These interactions are essential for Toll-like receptor-, RIG-I-, and Listeria-mediated expression of proinflammatory genes including Il6 and Il12b in macrophages. Consistently, effective clearance of Listeria infection required Akirin2. Furthermore, Akirin2 and IκB-ζ recruitment to the Il6 promoter depend upon the presence of IκB-ζ and Akirin2, respectively, for regulation of chromatin remodeling. BAF60 proteins were also essential for the induction of Il6 in response to LPS stimulation. Collectively, the IκB-ζ-Akirin2-BAF60 complex physically links the NF-κB and SWI/SNF complexes in innate immune cell activation. By recruiting SWI/SNF chromatin remodellers to IκB-ζ, transcriptional coactivator for NF-κB, the conserved nuclear protein Akirin2 stimulates pro-inflammatory gene promoters in mouse macrophages during innate immune responses to viral or bacterial infection.},
keywords = {Adaptor Proteins, Animals, Cell Nucleus, Chromatin Assembly and Disassembly, chromatin remodeling, Chromosomal Proteins, cytokine, Cytokines, Female, Gene Expression Regulation, gene regulation, Genetic, hoffmann, Humans, Immunity, Innate, innate immunity, Knockout, Listeria monocytogenes, M3i, Macrophages, Male, Mice, Multiprotein Complexes, Non-Histone, Nuclear Proteins, Promoter Regions, Protein Binding, reichhart, Repressor Proteins, Sequence Deletion, Signal Transducing, Transcriptional Activation},
pubstate = {published},
tppubtype = {article}
}
Transcription of inflammatory genes in innate immune cells is coordinately regulated by transcription factors, including NF-κB, and chromatin modifiers. However, it remains unclear how microbial sensing initiates chromatin remodeling. Here, we show that Akirin2, an evolutionarily conserved nuclear protein, bridges NF-κB and the chromatin remodeling SWI/SNF complex by interacting with BRG1-Associated Factor 60 (BAF60) proteins as well as IκB-ζ, which forms a complex with the NF-κB p50 subunit. These interactions are essential for Toll-like receptor-, RIG-I-, and Listeria-mediated expression of proinflammatory genes including Il6 and Il12b in macrophages. Consistently, effective clearance of Listeria infection required Akirin2. Furthermore, Akirin2 and IκB-ζ recruitment to the Il6 promoter depend upon the presence of IκB-ζ and Akirin2, respectively, for regulation of chromatin remodeling. BAF60 proteins were also essential for the induction of Il6 in response to LPS stimulation. Collectively, the IκB-ζ-Akirin2-BAF60 complex physically links the NF-κB and SWI/SNF complexes in innate immune cell activation. By recruiting SWI/SNF chromatin remodellers to IκB-ζ, transcriptional coactivator for NF-κB, the conserved nuclear protein Akirin2 stimulates pro-inflammatory gene promoters in mouse macrophages during innate immune responses to viral or bacterial infection.
Leclerc Vincent, Chamy Laure El, Ntwasa Monde, Reichhart Jean-Marc
Drosophila melanogaster model in innate immunity. Article de journal
Dans: Trends in Entomology, vol. 10, p. 73–86, 2014.
Résumé | BibTeX | Étiquettes: M3i, reichhart
@article{leclerc_drosophila_2014,
title = {Drosophila melanogaster model in innate immunity.},
author = {Vincent Leclerc and Laure El Chamy and Monde Ntwasa and Jean-Marc Reichhart},
year = {2014},
date = {2014-01-01},
journal = {Trends in Entomology},
volume = {10},
pages = {73--86},
abstract = {Due relative simplicity of the fly and availability of large amounts of genetic tools, Drosophila melanogaster has proven to be an excellent model to study the basic principles of innate immunity. This is illustrated by the discovery of the Toll-like receptor functions in pathogen sensing, recognised by the 2011 Nobel Prize in Physiology and Medicine awarded to Jules Hoffmann. Drosophila can also be used as an in vivo, genetically tractable model, to analyse various aspects of host-pathogen interactions including virulence factor mechanisms of action.},
keywords = {M3i, reichhart},
pubstate = {published},
tppubtype = {article}
}
Due relative simplicity of the fly and availability of large amounts of genetic tools, Drosophila melanogaster has proven to be an excellent model to study the basic principles of innate immunity. This is illustrated by the discovery of the Toll-like receptor functions in pathogen sensing, recognised by the 2011 Nobel Prize in Physiology and Medicine awarded to Jules Hoffmann. Drosophila can also be used as an in vivo, genetically tractable model, to analyse various aspects of host-pathogen interactions including virulence factor mechanisms of action.
2013
Kobayashi Taira, Ogawa Michinaga, Sanada Takahito, Mimuro Hitomi, Kim Minsoo, Ashida Hiroshi, Akakura Reiko, Yoshida Mitsutaka, Kawalec Magdalena, Reichhart Jean-Marc, Mizushima Tsunehiro, Sasakawa Chihiro
The Shigella OspC3 effector inhibits caspase-4, antagonizes inflammatory cell death, and promotes epithelial infection Article de journal
Dans: Cell Host Microbe, vol. 13, no. 5, p. 570–583, 2013, ISSN: 1934-6069.
Résumé | Liens | BibTeX | Étiquettes: Animal, Animals, Bacillary, Bacterial, Bacterial Proteins, Caspases, Cell Death, Cell Line, Disease Models, DNA, Dysentery, Enzyme Inhibitors, Epithelial Cells, Escherichia coli, Gene Knockout Techniques, Guinea Pigs, Host-Pathogen Interactions, Humans, Initiator, M3i, Protein Binding, Protein Interaction Mapping, reichhart, Salmonella typhimurium, Sequence Analysis, Shigella flexneri, Virulence Factors
@article{kobayashi_shigella_2013,
title = {The Shigella OspC3 effector inhibits caspase-4, antagonizes inflammatory cell death, and promotes epithelial infection},
author = {Taira Kobayashi and Michinaga Ogawa and Takahito Sanada and Hitomi Mimuro and Minsoo Kim and Hiroshi Ashida and Reiko Akakura and Mitsutaka Yoshida and Magdalena Kawalec and Jean-Marc Reichhart and Tsunehiro Mizushima and Chihiro Sasakawa},
doi = {10.1016/j.chom.2013.04.012},
issn = {1934-6069},
year = {2013},
date = {2013-05-01},
journal = {Cell Host Microbe},
volume = {13},
number = {5},
pages = {570--583},
abstract = {Caspase-mediated inflammatory cell death acts as an intrinsic defense mechanism against infection. Bacterial pathogens deploy countermeasures against inflammatory cell death, but the mechanisms by which they do this remain largely unclear. In a screen for Shigella flexneri effectors that regulate cell death during infection, we discovered that Shigella infection induced acute inflammatory, caspase-4-dependent epithelial cell death, which is counteracted by the bacterial OspC3 effector. OspC3 interacts with the caspase-4-p19 subunit and inhibits its activation by preventing caspase-4-p19 and caspase-4-p10 heterodimerization by depositing the conserved OspC3 X1-Y-X₂-D-X₃ motif at the putative catalytic pocket of caspase-4. Infection of guinea pigs with a Shigella ospC3-deficient mutant resulted in enhanced inflammatory cell death and associated symptoms, correlating with decreased bacterial burdens. Salmonella Typhimurium and enteropathogenic Escherichia coli infection also induced caspase-4-dependent epithelial death. These findings highlight the importance of caspase-4-dependent innate immune responses and demonstrate that Shigella delivers a caspase-4-specific inhibitor to delay epithelial cell death and promote infection.},
keywords = {Animal, Animals, Bacillary, Bacterial, Bacterial Proteins, Caspases, Cell Death, Cell Line, Disease Models, DNA, Dysentery, Enzyme Inhibitors, Epithelial Cells, Escherichia coli, Gene Knockout Techniques, Guinea Pigs, Host-Pathogen Interactions, Humans, Initiator, M3i, Protein Binding, Protein Interaction Mapping, reichhart, Salmonella typhimurium, Sequence Analysis, Shigella flexneri, Virulence Factors},
pubstate = {published},
tppubtype = {article}
}
Caspase-mediated inflammatory cell death acts as an intrinsic defense mechanism against infection. Bacterial pathogens deploy countermeasures against inflammatory cell death, but the mechanisms by which they do this remain largely unclear. In a screen for Shigella flexneri effectors that regulate cell death during infection, we discovered that Shigella infection induced acute inflammatory, caspase-4-dependent epithelial cell death, which is counteracted by the bacterial OspC3 effector. OspC3 interacts with the caspase-4-p19 subunit and inhibits its activation by preventing caspase-4-p19 and caspase-4-p10 heterodimerization by depositing the conserved OspC3 X1-Y-X₂-D-X₃ motif at the putative catalytic pocket of caspase-4. Infection of guinea pigs with a Shigella ospC3-deficient mutant resulted in enhanced inflammatory cell death and associated symptoms, correlating with decreased bacterial burdens. Salmonella Typhimurium and enteropathogenic Escherichia coli infection also induced caspase-4-dependent epithelial death. These findings highlight the importance of caspase-4-dependent innate immune responses and demonstrate that Shigella delivers a caspase-4-specific inhibitor to delay epithelial cell death and promote infection.
Bonnay François, Cohen-Berros Eva, Hoffmann Martine, Kim Sabrina Y, Boulianne Gabrielle L, Hoffmann Jules A, Matt Nicolas, Reichhart Jean-Marc
Big bang gene modulates gut immune tolerance in Drosophila Article de journal
Dans: Proc. Natl. Acad. Sci. U.S.A., vol. 110, no. 8, p. 2957–2962, 2013, ISSN: 1091-6490.
Résumé | Liens | BibTeX | Étiquettes: Animals, hoffmann, Immune Tolerance, Longevity, M3i, matt, Membrane Proteins, reichhart
@article{bonnay_big_2013,
title = {Big bang gene modulates gut immune tolerance in Drosophila},
author = {François Bonnay and Eva Cohen-Berros and Martine Hoffmann and Sabrina Y Kim and Gabrielle L Boulianne and Jules A Hoffmann and Nicolas Matt and Jean-Marc Reichhart},
doi = {10.1073/pnas.1221910110},
issn = {1091-6490},
year = {2013},
date = {2013-02-01},
journal = {Proc. Natl. Acad. Sci. U.S.A.},
volume = {110},
number = {8},
pages = {2957--2962},
abstract = {Chronic inflammation of the intestine is detrimental to mammals. Similarly, constant activation of the immune response in the gut by the endogenous flora is suspected to be harmful to Drosophila. Therefore, the innate immune response in the gut of Drosophila melanogaster is tightly balanced to simultaneously prevent infections by pathogenic microorganisms and tolerate the endogenous flora. Here we describe the role of the big bang (bbg) gene, encoding multiple membrane-associated PDZ (PSD-95, Discs-large, ZO-1) domain-containing protein isoforms, in the modulation of the gut immune response. We show that in the adult Drosophila midgut, BBG is present at the level of the septate junctions, on the apical side of the enterocytes. In the absence of BBG, these junctions become loose, enabling the intestinal flora to trigger a constitutive activation of the anterior midgut immune response. This chronic epithelial inflammation leads to a reduced lifespan of bbg mutant flies. Clearing the commensal flora by antibiotics prevents the abnormal activation of the gut immune response and restores a normal lifespan. We now provide genetic evidence that Drosophila septate junctions are part of the gut immune barrier, a function that is evolutionarily conserved in mammals. Collectively, our data suggest that septate junctions are required to maintain the subtle balance between immune tolerance and immune response in the Drosophila gut, which represents a powerful model to study inflammatory bowel diseases.},
keywords = {Animals, hoffmann, Immune Tolerance, Longevity, M3i, matt, Membrane Proteins, reichhart},
pubstate = {published},
tppubtype = {article}
}
Chronic inflammation of the intestine is detrimental to mammals. Similarly, constant activation of the immune response in the gut by the endogenous flora is suspected to be harmful to Drosophila. Therefore, the innate immune response in the gut of Drosophila melanogaster is tightly balanced to simultaneously prevent infections by pathogenic microorganisms and tolerate the endogenous flora. Here we describe the role of the big bang (bbg) gene, encoding multiple membrane-associated PDZ (PSD-95, Discs-large, ZO-1) domain-containing protein isoforms, in the modulation of the gut immune response. We show that in the adult Drosophila midgut, BBG is present at the level of the septate junctions, on the apical side of the enterocytes. In the absence of BBG, these junctions become loose, enabling the intestinal flora to trigger a constitutive activation of the anterior midgut immune response. This chronic epithelial inflammation leads to a reduced lifespan of bbg mutant flies. Clearing the commensal flora by antibiotics prevents the abnormal activation of the gut immune response and restores a normal lifespan. We now provide genetic evidence that Drosophila septate junctions are part of the gut immune barrier, a function that is evolutionarily conserved in mammals. Collectively, our data suggest that septate junctions are required to maintain the subtle balance between immune tolerance and immune response in the Drosophila gut, which represents a powerful model to study inflammatory bowel diseases.
Baron Olga Lucia, van West Pieter, Industri Benoit, Ponchet Michel, Dubreuil Géraldine, Gourbal Benjamin, Reichhart Jean-Marc, Coustau Christine
Parental transfer of the antimicrobial protein LBP/BPI protects Biomphalaria glabrata eggs against oomycete infections Article de journal
Dans: PLoS Pathog., vol. 9, no. 12, p. e1003792, 2013, ISSN: 1553-7374.
Résumé | Liens | BibTeX | Étiquettes: Acute-Phase Proteins, Animals, Antimicrobial Cationic Peptides, Biomphalaria, Blood Proteins, Carrier Proteins, Cell Membrane, Cell Membrane Permeability, Cloning, Escherichia coli, Female, Immunity, infection, M3i, Maternally-Acquired, Membrane Glycoproteins, Microbial Sensitivity Tests, Molecular, Oomycetes, Recombinant Proteins, reichhart, Zygote
@article{baron_parental_2013,
title = {Parental transfer of the antimicrobial protein LBP/BPI protects Biomphalaria glabrata eggs against oomycete infections},
author = {Olga Lucia Baron and Pieter van West and Benoit Industri and Michel Ponchet and Géraldine Dubreuil and Benjamin Gourbal and Jean-Marc Reichhart and Christine Coustau},
doi = {10.1371/journal.ppat.1003792},
issn = {1553-7374},
year = {2013},
date = {2013-01-01},
journal = {PLoS Pathog.},
volume = {9},
number = {12},
pages = {e1003792},
abstract = {Vertebrate females transfer antibodies via the placenta, colostrum and milk or via the egg yolk to protect their immunologically immature offspring against pathogens. This evolutionarily important transfer of immunity is poorly documented in invertebrates and basic questions remain regarding the nature and extent of parental protection of offspring. In this study, we show that a lipopolysaccharide binding protein/bactericidal permeability increasing protein family member from the invertebrate Biomphalaria glabrata (BgLBP/BPI1) is massively loaded into the eggs of this freshwater snail. Native and recombinant proteins displayed conserved LPS-binding, antibacterial and membrane permeabilizing activities. A broad screening of various pathogens revealed a previously unknown biocidal activity of the protein against pathogenic water molds (oomycetes), which is conserved in human BPI. RNAi-dependent silencing of LBP/BPI in the parent snails resulted in a significant reduction of reproductive success and extensive death of eggs through oomycete infections. This work provides the first functional evidence that a LBP/BPI is involved in the parental immune protection of invertebrate offspring and reveals a novel and conserved biocidal activity for LBP/BPI family members.},
keywords = {Acute-Phase Proteins, Animals, Antimicrobial Cationic Peptides, Biomphalaria, Blood Proteins, Carrier Proteins, Cell Membrane, Cell Membrane Permeability, Cloning, Escherichia coli, Female, Immunity, infection, M3i, Maternally-Acquired, Membrane Glycoproteins, Microbial Sensitivity Tests, Molecular, Oomycetes, Recombinant Proteins, reichhart, Zygote},
pubstate = {published},
tppubtype = {article}
}
Vertebrate females transfer antibodies via the placenta, colostrum and milk or via the egg yolk to protect their immunologically immature offspring against pathogens. This evolutionarily important transfer of immunity is poorly documented in invertebrates and basic questions remain regarding the nature and extent of parental protection of offspring. In this study, we show that a lipopolysaccharide binding protein/bactericidal permeability increasing protein family member from the invertebrate Biomphalaria glabrata (BgLBP/BPI1) is massively loaded into the eggs of this freshwater snail. Native and recombinant proteins displayed conserved LPS-binding, antibacterial and membrane permeabilizing activities. A broad screening of various pathogens revealed a previously unknown biocidal activity of the protein against pathogenic water molds (oomycetes), which is conserved in human BPI. RNAi-dependent silencing of LBP/BPI in the parent snails resulted in a significant reduction of reproductive success and extensive death of eggs through oomycete infections. This work provides the first functional evidence that a LBP/BPI is involved in the parental immune protection of invertebrate offspring and reveals a novel and conserved biocidal activity for LBP/BPI family members.
2012
Ezekowitz Alan R B, Dimarcq Jean-Luc, Kafatos Fotis, Levashina Elena A, Ferrandon Dominique, Hetru Charles, Imler Jean-Luc, Reichhart Jean-Marc
Lawrence's book review unfair to Hoffmann Article de journal
Dans: Curr. Biol., vol. 22, no. 12, p. R482, 2012, ISSN: 1879-0445.
Liens | BibTeX | Étiquettes: Book Reviews as Topic, Ethics, ferrandon, imler, M3i, Professional, reichhart
@article{ezekowitz_lawrences_2012,
title = {Lawrence's book review unfair to Hoffmann},
author = {Alan R B Ezekowitz and Jean-Luc Dimarcq and Fotis Kafatos and Elena A Levashina and Dominique Ferrandon and Charles Hetru and Jean-Luc Imler and Jean-Marc Reichhart},
doi = {10.1016/j.cub.2012.05.015},
issn = {1879-0445},
year = {2012},
date = {2012-06-01},
journal = {Curr. Biol.},
volume = {22},
number = {12},
pages = {R482},
keywords = {Book Reviews as Topic, Ethics, ferrandon, imler, M3i, Professional, reichhart},
pubstate = {published},
tppubtype = {article}
}
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
Dans: J. Immunol., vol. 188, no. 11, p. 5210–5220, 2012, ISSN: 1550-6606.
Résumé | BibTeX | Étiquettes: Animals, Antifungal Agents, Developmental, DNA-Binding Proteins, Gene Expression Regulation, history, hoffmann, M3i, Multigene Family, Mycoses, Phosphoproteins, reichhart, 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 = {Animals, Antifungal Agents, Developmental, DNA-Binding Proteins, Gene Expression Regulation, history, hoffmann, M3i, Multigene Family, Mycoses, Phosphoproteins, reichhart, 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.
Deleury Emeline, Dubreuil Géraldine, Elangovan Namasivayam, Wajnberg Eric, Reichhart Jean-Marc, Gourbal Benjamin, Duval David, Baron Olga Lucia, Gouzy Jérôme, Coustau Christine
Specific versus non-specific immune responses in an invertebrate species evidenced by a comparative de novo sequencing study Article de journal
Dans: PLoS ONE, vol. 7, no. 3, p. e32512, 2012, ISSN: 1932-6203.
Résumé | Liens | BibTeX | Étiquettes: Animals, Biomphalaria, Calmodulin, Cluster Analysis, Complementary, DNA, Expressed Sequence Tags, Ferritins, Gene Expression Profiling, Gene Expression Regulation, High-Throughput Nucleotide Sequencing, Immunity, Innate, M3i, messenger, Pattern Recognition, Phylogeny, Receptors, reichhart, RNA, Signal Transduction, Zinc Fingers
@article{deleury_specific_2012,
title = {Specific versus non-specific immune responses in an invertebrate species evidenced by a comparative de novo sequencing study},
author = {Emeline Deleury and Géraldine Dubreuil and Namasivayam Elangovan and Eric Wajnberg and Jean-Marc Reichhart and Benjamin Gourbal and David Duval and Olga Lucia Baron and Jérôme Gouzy and Christine Coustau},
doi = {10.1371/journal.pone.0032512},
issn = {1932-6203},
year = {2012},
date = {2012-01-01},
journal = {PLoS ONE},
volume = {7},
number = {3},
pages = {e32512},
abstract = {Our present understanding of the functioning and evolutionary history of invertebrate innate immunity derives mostly from studies on a few model species belonging to ecdysozoa. In particular, the characterization of signaling pathways dedicated to specific responses towards fungi and Gram-positive or Gram-negative bacteria in Drosophila melanogaster challenged our original view of a non-specific immunity in invertebrates. However, much remains to be elucidated from lophotrochozoan species. To investigate the global specificity of the immune response in the fresh-water snail Biomphalaria glabrata, we used massive Illumina sequencing of 5'-end cDNAs to compare expression profiles after challenge by Gram-positive or Gram-negative bacteria or after a yeast challenge. 5'-end cDNA sequencing of the libraries yielded over 12 millions high quality reads. To link these short reads to expressed genes, we prepared a reference transcriptomic database through automatic assembly and annotation of the 758,510 redundant sequences (ESTs, mRNAs) of B. glabrata available in public databases. Computational analysis of Illumina reads followed by multivariate analyses allowed identification of 1685 candidate transcripts differentially expressed after an immune challenge, with a two fold ratio between transcripts showing a challenge-specific expression versus a lower or non-specific differential expression. Differential expression has been validated using quantitative PCR for a subset of randomly selected candidates. Predicted functions of annotated candidates (approx. 700 unisequences) belonged to a large extend to similar functional categories or protein types. This work significantly expands upon previous gene discovery and expression studies on B. glabrata and suggests that responses to various pathogens may involve similar immune processes or signaling pathways but different genes belonging to multigenic families. These results raise the question of the importance of gene duplication and acquisition of paralog functional diversity in the evolution of specific invertebrate immune responses.},
keywords = {Animals, Biomphalaria, Calmodulin, Cluster Analysis, Complementary, DNA, Expressed Sequence Tags, Ferritins, Gene Expression Profiling, Gene Expression Regulation, High-Throughput Nucleotide Sequencing, Immunity, Innate, M3i, messenger, Pattern Recognition, Phylogeny, Receptors, reichhart, RNA, Signal Transduction, Zinc Fingers},
pubstate = {published},
tppubtype = {article}
}
Our present understanding of the functioning and evolutionary history of invertebrate innate immunity derives mostly from studies on a few model species belonging to ecdysozoa. In particular, the characterization of signaling pathways dedicated to specific responses towards fungi and Gram-positive or Gram-negative bacteria in Drosophila melanogaster challenged our original view of a non-specific immunity in invertebrates. However, much remains to be elucidated from lophotrochozoan species. To investigate the global specificity of the immune response in the fresh-water snail Biomphalaria glabrata, we used massive Illumina sequencing of 5'-end cDNAs to compare expression profiles after challenge by Gram-positive or Gram-negative bacteria or after a yeast challenge. 5'-end cDNA sequencing of the libraries yielded over 12 millions high quality reads. To link these short reads to expressed genes, we prepared a reference transcriptomic database through automatic assembly and annotation of the 758,510 redundant sequences (ESTs, mRNAs) of B. glabrata available in public databases. Computational analysis of Illumina reads followed by multivariate analyses allowed identification of 1685 candidate transcripts differentially expressed after an immune challenge, with a two fold ratio between transcripts showing a challenge-specific expression versus a lower or non-specific differential expression. Differential expression has been validated using quantitative PCR for a subset of randomly selected candidates. Predicted functions of annotated candidates (approx. 700 unisequences) belonged to a large extend to similar functional categories or protein types. This work significantly expands upon previous gene discovery and expression studies on B. glabrata and suggests that responses to various pathogens may involve similar immune processes or signaling pathways but different genes belonging to multigenic families. These results raise the question of the importance of gene duplication and acquisition of paralog functional diversity in the evolution of specific invertebrate immune responses.
2011
Boyer Laurent, Magoc Lorin, Dejardin Stephanie, Cappillino Michael, Paquette Nicholas, Hinault Charlotte, Charriere Guillaume M, Ip Eddie W K, Fracchia Shannon, Hennessy Elizabeth, Erturk-Hasdemir Deniz, Reichhart Jean-Marc, Silverman Neal, Lacy-Hulbert Adam, Stuart Lynda M
Pathogen-derived effectors trigger protective immunity via activation of the Rac2 enzyme and the IMD or Rip kinase signaling pathway Article de journal
Dans: Immunity, vol. 35, no. 4, p. 536–549, 2011, ISSN: 1097-4180.
Résumé | Liens | BibTeX | Étiquettes: Adaptor Proteins, Enzyme Activation, HEK293 Cells, Humans, M3i, rac GTP-Binding Proteins, Receptor-Interacting Protein Serine-Threonine Kinases, reichhart, Signal Transducing, Signal Transduction
@article{boyer_pathogen-derived_2011,
title = {Pathogen-derived effectors trigger protective immunity via activation of the Rac2 enzyme and the IMD or Rip kinase signaling pathway},
author = {Laurent Boyer and Lorin Magoc and Stephanie Dejardin and Michael Cappillino and Nicholas Paquette and Charlotte Hinault and Guillaume M Charriere and Eddie W K Ip and Shannon Fracchia and Elizabeth Hennessy and Deniz Erturk-Hasdemir and Jean-Marc Reichhart and Neal Silverman and Adam Lacy-Hulbert and Lynda M Stuart},
doi = {10.1016/j.immuni.2011.08.015},
issn = {1097-4180},
year = {2011},
date = {2011-10-01},
journal = {Immunity},
volume = {35},
number = {4},
pages = {536--549},
abstract = {Although infections with virulent pathogens often induce a strong inflammatory reaction, what drives the increased immune response to pathogens compared to nonpathogenic microbes is poorly understood. One possibility is that the immune system senses the level of threat from a microorganism and augments the response accordingly. Here, focusing on cytotoxic necrotizing factor 1 (CNF1), an Escherichia coli-derived effector molecule, we showed the host indirectly sensed the pathogen by monitoring for the effector that modified RhoGTPases. CNF1 modified Rac2, which then interacted with the innate immune adaptors IMD and Rip1-Rip2 in flies and mammalian cells, respectively, to drive an immune response. This response was protective and increased the ability of the host to restrict pathogen growth, thus defining a mechanism of effector-triggered immunity that contributes to how metazoans defend against microbes with pathogenic potential.},
keywords = {Adaptor Proteins, Enzyme Activation, HEK293 Cells, Humans, M3i, rac GTP-Binding Proteins, Receptor-Interacting Protein Serine-Threonine Kinases, reichhart, Signal Transducing, Signal Transduction},
pubstate = {published},
tppubtype = {article}
}
Although infections with virulent pathogens often induce a strong inflammatory reaction, what drives the increased immune response to pathogens compared to nonpathogenic microbes is poorly understood. One possibility is that the immune system senses the level of threat from a microorganism and augments the response accordingly. Here, focusing on cytotoxic necrotizing factor 1 (CNF1), an Escherichia coli-derived effector molecule, we showed the host indirectly sensed the pathogen by monitoring for the effector that modified RhoGTPases. CNF1 modified Rac2, which then interacted with the innate immune adaptors IMD and Rip1-Rip2 in flies and mammalian cells, respectively, to drive an immune response. This response was protective and increased the ability of the host to restrict pathogen growth, thus defining a mechanism of effector-triggered immunity that contributes to how metazoans defend against microbes with pathogenic potential.
Ogawa Michinaga, Yoshikawa Yuko, Kobayashi Taira, Mimuro Hitomi, Fukumatsu Makoto, Kiga Kotaro, Piao Zhenzi, Ashida Hiroshi, Yoshida Mitsutaka, Kakuta Shigeru, Koyama Tomohiro, Goto Yoshiyuki, Nagatake Takahiro, Nagai Shinya, Kiyono Hiroshi, Kawalec Magdalena, Reichhart Jean-Marc, Sasakawa Chihiro
A Tecpr1-dependent selective autophagy pathway targets bacterial pathogens Article de journal
Dans: Cell Host Microbe, vol. 9, no. 5, p. 376–389, 2011, ISSN: 1934-6069.
Résumé | Liens | BibTeX | Étiquettes: Animals, Autophagy, Biological, Cells, Cultured, M3i, Membrane Proteins, Mice, Microtubule-Associated Proteins, Models, Phagosomes, Protein Interaction Mapping, reichhart, Shigella, Two-Hybrid System Techniques
@article{ogawa_tecpr1-dependent_2011,
title = {A Tecpr1-dependent selective autophagy pathway targets bacterial pathogens},
author = {Michinaga Ogawa and Yuko Yoshikawa and Taira Kobayashi and Hitomi Mimuro and Makoto Fukumatsu and Kotaro Kiga and Zhenzi Piao and Hiroshi Ashida and Mitsutaka Yoshida and Shigeru Kakuta and Tomohiro Koyama and Yoshiyuki Goto and Takahiro Nagatake and Shinya Nagai and Hiroshi Kiyono and Magdalena Kawalec and Jean-Marc Reichhart and Chihiro Sasakawa},
doi = {10.1016/j.chom.2011.04.010},
issn = {1934-6069},
year = {2011},
date = {2011-05-01},
journal = {Cell Host Microbe},
volume = {9},
number = {5},
pages = {376--389},
abstract = {Selective autophagy of bacterial pathogens represents a host innate immune mechanism. Selective autophagy has been characterized on the basis of distinct cargo receptors but the mechanisms by which different cargo receptors are targeted for autophagic degradation remain unclear. In this study we identified a highly conserved Tectonin domain-containing protein, Tecpr1, as an Atg5 binding partner that colocalized with Atg5 at Shigella-containing phagophores. Tecpr1 activity is necessary for efficient autophagic targeting of bacteria, but has no effect on rapamycin- or starvation-induced canonical autophagy. Tecpr1 interacts with WIPI-2, a yeast Atg18 homolog and PI(3)P-interacting protein required for phagophore formation, and they colocalize to phagophores. Although Tecpr1-deficient mice appear normal, Tecpr1-deficient MEFs were defective for selective autophagy and supported increased intracellular multiplication of Shigella. Further, depolarized mitochondria and misfolded protein aggregates accumulated in the Tecpr1-knockout MEFs. Thus, we identify a Tecpr1-dependent pathway as important in targeting bacterial pathogens for selective autophagy.},
keywords = {Animals, Autophagy, Biological, Cells, Cultured, M3i, Membrane Proteins, Mice, Microtubule-Associated Proteins, Models, Phagosomes, Protein Interaction Mapping, reichhart, Shigella, Two-Hybrid System Techniques},
pubstate = {published},
tppubtype = {article}
}
Selective autophagy of bacterial pathogens represents a host innate immune mechanism. Selective autophagy has been characterized on the basis of distinct cargo receptors but the mechanisms by which different cargo receptors are targeted for autophagic degradation remain unclear. In this study we identified a highly conserved Tectonin domain-containing protein, Tecpr1, as an Atg5 binding partner that colocalized with Atg5 at Shigella-containing phagophores. Tecpr1 activity is necessary for efficient autophagic targeting of bacteria, but has no effect on rapamycin- or starvation-induced canonical autophagy. Tecpr1 interacts with WIPI-2, a yeast Atg18 homolog and PI(3)P-interacting protein required for phagophore formation, and they colocalize to phagophores. Although Tecpr1-deficient mice appear normal, Tecpr1-deficient MEFs were defective for selective autophagy and supported increased intracellular multiplication of Shigella. Further, depolarized mitochondria and misfolded protein aggregates accumulated in the Tecpr1-knockout MEFs. Thus, we identify a Tecpr1-dependent pathway as important in targeting bacterial pathogens for selective autophagy.
Kellenberger Christine, Leone Philippe, Coquet Laurent, Jouenne Thierry, Reichhart Jean-Marc, Roussel Alain
Structure-function analysis of grass clip serine protease involved in Drosophila Toll pathway activation Article de journal
Dans: J. Biol. Chem., vol. 286, no. 14, p. 12300–12307, 2011, ISSN: 1083-351X.
Résumé | Liens | BibTeX | Étiquettes: Animals, Catalytic Domain, Cell Line, M3i, reichhart, Serine Proteases, Signal Transduction, Structure-Activity Relationship, Toll-Like Receptors
@article{kellenberger_structure-function_2011,
title = {Structure-function analysis of grass clip serine protease involved in Drosophila Toll pathway activation},
author = {Christine Kellenberger and Philippe Leone and Laurent Coquet and Thierry Jouenne and Jean-Marc Reichhart and Alain Roussel},
doi = {10.1074/jbc.M110.182741},
issn = {1083-351X},
year = {2011},
date = {2011-04-01},
journal = {J. Biol. Chem.},
volume = {286},
number = {14},
pages = {12300--12307},
abstract = {Grass is a clip domain serine protease (SP) involved in a proteolytic cascade triggering the Toll pathway activation of Drosophila during an immune response. Epistasic studies position it downstream of the apical protease ModSP and upstream of the terminal protease Spaetzle-processing enzyme. Here, we report the crystal structure of Grass zymogen. We found that Grass displays a rather deep active site cleft comparable with that of proteases of coagulation and complement cascades. A key distinctive feature is the presence of an additional loop (75-loop) in the proximity of the activation site localized on a protruding loop. All biochemical attempts to hydrolyze the activation site of Grass failed, strongly suggesting restricted access to this region. The 75-loop is thus proposed to constitute an original mechanism to prevent spontaneous activation. A comparison of Grass with clip serine proteases of known function involved in analogous proteolytic cascades allowed us to define two groups, according to the presence of the 75-loop and the conformation of the clip domain. One group (devoid of the 75-loop) contains penultimate proteases whereas the other contains terminal proteases. Using this classification, Grass appears to be a terminal protease. This result is evaluated according to the genetic data documenting Grass function.},
keywords = {Animals, Catalytic Domain, Cell Line, M3i, reichhart, Serine Proteases, Signal Transduction, Structure-Activity Relationship, Toll-Like Receptors},
pubstate = {published},
tppubtype = {article}
}
Grass is a clip domain serine protease (SP) involved in a proteolytic cascade triggering the Toll pathway activation of Drosophila during an immune response. Epistasic studies position it downstream of the apical protease ModSP and upstream of the terminal protease Spaetzle-processing enzyme. Here, we report the crystal structure of Grass zymogen. We found that Grass displays a rather deep active site cleft comparable with that of proteases of coagulation and complement cascades. A key distinctive feature is the presence of an additional loop (75-loop) in the proximity of the activation site localized on a protruding loop. All biochemical attempts to hydrolyze the activation site of Grass failed, strongly suggesting restricted access to this region. The 75-loop is thus proposed to constitute an original mechanism to prevent spontaneous activation. A comparison of Grass with clip serine proteases of known function involved in analogous proteolytic cascades allowed us to define two groups, according to the presence of the 75-loop and the conformation of the clip domain. One group (devoid of the 75-loop) contains penultimate proteases whereas the other contains terminal proteases. Using this classification, Grass appears to be a terminal protease. This result is evaluated according to the genetic data documenting Grass function.
Reichhart Jean-Marc, Gubb David, Leclerc Vincent
The Drosophila serpins: multiple functions in immunity and morphogenesis Article de journal
Dans: Meth. Enzymol., vol. 499, p. 205–225, 2011, ISSN: 1557-7988.
Résumé | Liens | BibTeX | Étiquettes: Animals, Immunity, Innate, M3i, Morphogenesis, reichhart, Serpins, Signal Transduction
@article{reichhart_drosophila_2011,
title = {The Drosophila serpins: multiple functions in immunity and morphogenesis},
author = {Jean-Marc Reichhart and David Gubb and Vincent Leclerc},
doi = {10.1016/B978-0-12-386471-0.00011-0},
issn = {1557-7988},
year = {2011},
date = {2011-01-01},
journal = {Meth. Enzymol.},
volume = {499},
pages = {205--225},
abstract = {Members of the serpin superfamily of proteins have been found in all living organisms, although rarely in bacteria or fungi. They have been extensively studied in mammals, where many rapid physiological responses are regulated by inhibitory serpins. In addition to the inhibitory serpins, a large group of noninhibitory proteins with a conserved serpin fold have also been identified in mammals. These noninhibitory proteins have a wide range of functions, from storage proteins to molecular chaperones, hormone transporters, and tumor suppressors. In contrast, until recently, very little was known about insect serpins in general, or Drosophila serpins in particular. In the last decade, however, there has been an increasing interest in the serpin biology of insects. It is becoming clear that, like in mammals, a similar wide range of physiological responses are regulated in insects and that noninhibitory serpin-fold proteins also play key roles in insect biology. Drosophila is also an important model organism that can be used to study human pathologies (among which serpinopathies or other protein conformational diseases) and mechanisms of regulation of proteolytic cascades in health or to develop strategies for control of insect pests and disease vectors. As most of our knowledge on insect serpins comes from studies on the Drosophila immune response, we survey here the Drosophila serpin literature and describe the laboratory techniques that have been developed to study serpin-regulated responses in this model genetic organism.},
keywords = {Animals, Immunity, Innate, M3i, Morphogenesis, reichhart, Serpins, Signal Transduction},
pubstate = {published},
tppubtype = {article}
}
Members of the serpin superfamily of proteins have been found in all living organisms, although rarely in bacteria or fungi. They have been extensively studied in mammals, where many rapid physiological responses are regulated by inhibitory serpins. In addition to the inhibitory serpins, a large group of noninhibitory proteins with a conserved serpin fold have also been identified in mammals. These noninhibitory proteins have a wide range of functions, from storage proteins to molecular chaperones, hormone transporters, and tumor suppressors. In contrast, until recently, very little was known about insect serpins in general, or Drosophila serpins in particular. In the last decade, however, there has been an increasing interest in the serpin biology of insects. It is becoming clear that, like in mammals, a similar wide range of physiological responses are regulated in insects and that noninhibitory serpin-fold proteins also play key roles in insect biology. Drosophila is also an important model organism that can be used to study human pathologies (among which serpinopathies or other protein conformational diseases) and mechanisms of regulation of proteolytic cascades in health or to develop strategies for control of insect pests and disease vectors. As most of our knowledge on insect serpins comes from studies on the Drosophila immune response, we survey here the Drosophila serpin literature and describe the laboratory techniques that have been developed to study serpin-regulated responses in this model genetic organism.
2010
Silverman Gary A, Whisstock James C, Bottomley Stephen P, Huntington James A, Kaiserman Dion, Luke Cliff J, Pak Stephen C, Reichhart Jean-Marc, Bird Phillip I
Serpins flex their muscle: I. Putting the clamps on proteolysis in diverse biological systems Article de journal
Dans: J. Biol. Chem., vol. 285, no. 32, p. 24299–24305, 2010, ISSN: 1083-351X.
Résumé | Liens | BibTeX | Étiquettes: Animals, Biological, Caenorhabditis elegans, Cell Death, Cell Differentiation, Cell Survival, Homeostasis, Humans, Immunity, Innate, M3i, Mice, Models, Phenotype, reichhart, Serpins, Transgenes, transgenic
@article{silverman_serpins_2010,
title = {Serpins flex their muscle: I. Putting the clamps on proteolysis in diverse biological systems},
author = {Gary A Silverman and James C Whisstock and Stephen P Bottomley and James A Huntington and Dion Kaiserman and Cliff J Luke and Stephen C Pak and Jean-Marc Reichhart and Phillip I Bird},
doi = {10.1074/jbc.R110.112771},
issn = {1083-351X},
year = {2010},
date = {2010-08-01},
journal = {J. Biol. Chem.},
volume = {285},
number = {32},
pages = {24299--24305},
abstract = {Serpins compose the largest superfamily of peptidase inhibitors and are well known as regulators of hemostasis and thrombolysis. Studies using model organisms, from plants to vertebrates, now show that serpins and their unique inhibitory mechanism and conformational flexibility are exploited to control proteolysis in molecular pathways associated with cell survival, development, and host defense. In addition, an increasing number of non-inhibitory serpins are emerging as important elements within a diversity of biological systems by serving as chaperones, hormone transporters, or anti-angiogenic factors.},
keywords = {Animals, Biological, Caenorhabditis elegans, Cell Death, Cell Differentiation, Cell Survival, Homeostasis, Humans, Immunity, Innate, M3i, Mice, Models, Phenotype, reichhart, Serpins, Transgenes, transgenic},
pubstate = {published},
tppubtype = {article}
}
Serpins compose the largest superfamily of peptidase inhibitors and are well known as regulators of hemostasis and thrombolysis. Studies using model organisms, from plants to vertebrates, now show that serpins and their unique inhibitory mechanism and conformational flexibility are exploited to control proteolysis in molecular pathways associated with cell survival, development, and host defense. In addition, an increasing number of non-inhibitory serpins are emerging as important elements within a diversity of biological systems by serving as chaperones, hormone transporters, or anti-angiogenic factors.
Whisstock James C, Silverman Gary A, Bird Phillip I, Bottomley Stephen P, Kaiserman Dion, Luke Cliff J, Pak Stephen C, Reichhart Jean-Marc, Huntington James A
Serpins flex their muscle: II. Structural insights into target peptidase recognition, polymerization, and transport functions Article de journal
Dans: J. Biol. Chem., vol. 285, no. 32, p. 24307–24312, 2010, ISSN: 1083-351X.
Résumé | Liens | BibTeX | Étiquettes: Animals, Biological, Biological Transport, Biophysics, Catalytic Domain, Hormones, Humans, Kinetics, M3i, Models, Peptide Hydrolases, Protein Binding, Protein Conformation, Protein Structure, reichhart, Serpins, Substrate Specificity, Tertiary, Thrombin
@article{whisstock_serpins_2010,
title = {Serpins flex their muscle: II. Structural insights into target peptidase recognition, polymerization, and transport functions},
author = {James C Whisstock and Gary A Silverman and Phillip I Bird and Stephen P Bottomley and Dion Kaiserman and Cliff J Luke and Stephen C Pak and Jean-Marc Reichhart and James A Huntington},
doi = {10.1074/jbc.R110.141408},
issn = {1083-351X},
year = {2010},
date = {2010-08-01},
journal = {J. Biol. Chem.},
volume = {285},
number = {32},
pages = {24307--24312},
abstract = {Inhibitory serpins are metastable proteins that undergo a substantial conformational rearrangement to covalently trap target peptidases. The serpin reactive center loop contributes a majority of the interactions that serpins make during the initial binding to target peptidases. However, structural studies on serpin-peptidase complexes reveal a broader set of contacts on the scaffold of inhibitory serpins that have substantial influence on guiding peptidase recognition. Structural and biophysical studies also reveal how aberrant serpin folding can lead to the formation of domain-swapped serpin multimers rather than the monomeric metastable state. Serpin domain swapping may therefore underlie the polymerization events characteristic of the serpinopathies. Finally, recent structural studies reveal how the serpin fold has been adapted for non-inhibitory functions such as hormone binding.},
keywords = {Animals, Biological, Biological Transport, Biophysics, Catalytic Domain, Hormones, Humans, Kinetics, M3i, Models, Peptide Hydrolases, Protein Binding, Protein Conformation, Protein Structure, reichhart, Serpins, Substrate Specificity, Tertiary, Thrombin},
pubstate = {published},
tppubtype = {article}
}
Inhibitory serpins are metastable proteins that undergo a substantial conformational rearrangement to covalently trap target peptidases. The serpin reactive center loop contributes a majority of the interactions that serpins make during the initial binding to target peptidases. However, structural studies on serpin-peptidase complexes reveal a broader set of contacts on the scaffold of inhibitory serpins that have substantial influence on guiding peptidase recognition. Structural and biophysical studies also reveal how aberrant serpin folding can lead to the formation of domain-swapped serpin multimers rather than the monomeric metastable state. Serpin domain swapping may therefore underlie the polymerization events characteristic of the serpinopathies. Finally, recent structural studies reveal how the serpin fold has been adapted for non-inhibitory functions such as hormone binding.
Garcia Alvaro Baeza, Pierce Raymond J, Gourbal Benjamin, Werkmeister Elisabeth, Colinet Dominique, Reichhart Jean-Marc, Dissous Colette, Coustau Christine
Involvement of the cytokine MIF in the snail host immune response to the parasite Schistosoma mansoni Article de journal
Dans: PLoS Pathog., vol. 6, no. 9, p. e1001115, 2010, ISSN: 1553-7374.
Résumé | Liens | BibTeX | Étiquettes: Amino Acid, Animals, Apoptosis, Biomphalaria, Blotting, Cell Proliferation, Cells, Cricetinae, Cultured, Hemocytes, Host-Parasite Interactions, Humans, Liver, M3i, Macrophage Migration-Inhibitory Factors, messenger, Oocysts, Recombinant Proteins, reichhart, Reverse Transcriptase Polymerase Chain Reaction, RNA, Schistosoma mansoni, Schistosomiasis mansoni, Sequence Homology, Small Interfering, Western
@article{baeza_garcia_involvement_2010,
title = {Involvement of the cytokine MIF in the snail host immune response to the parasite Schistosoma mansoni},
author = {Alvaro Baeza Garcia and Raymond J Pierce and Benjamin Gourbal and Elisabeth Werkmeister and Dominique Colinet and Jean-Marc Reichhart and Colette Dissous and Christine Coustau},
doi = {10.1371/journal.ppat.1001115},
issn = {1553-7374},
year = {2010},
date = {2010-01-01},
journal = {PLoS Pathog.},
volume = {6},
number = {9},
pages = {e1001115},
abstract = {We have identified and characterized a Macrophage Migration Inhibitory Factor (MIF) family member in the Lophotrochozoan invertebrate, Biomphalaria glabrata, the snail intermediate host of the human blood fluke Schistosoma mansoni. In mammals, MIF is a widely expressed pleiotropic cytokine with potent pro-inflammatory properties that controls cell functions such as gene expression, proliferation or apoptosis. Here we show that the MIF protein from B. glabrata (BgMIF) is expressed in circulating immune defense cells (hemocytes) of the snail as well as in the B. glabrata embryonic (Bge) cell line that has hemocyte-like features. Recombinant BgMIF (rBgMIF) induced cell proliferation and inhibited NO-dependent p53-mediated apoptosis in Bge cells. Moreover, knock-down of BgMIF expression in Bge cells interfered with the in vitro encapsulation of S. mansoni sporocysts. Furthermore, the in vivo knock-down of BgMIF prevented the changes in circulating hemocyte populations that occur in response to an infection by S. mansoni miracidia and led to a significant increase in the parasite burden of the snails. These results provide the first functional evidence that a MIF ortholog is involved in an invertebrate immune response towards a parasitic infection and highlight the importance of cytokines in invertebrate-parasite interactions.},
keywords = {Amino Acid, Animals, Apoptosis, Biomphalaria, Blotting, Cell Proliferation, Cells, Cricetinae, Cultured, Hemocytes, Host-Parasite Interactions, Humans, Liver, M3i, Macrophage Migration-Inhibitory Factors, messenger, Oocysts, Recombinant Proteins, reichhart, Reverse Transcriptase Polymerase Chain Reaction, RNA, Schistosoma mansoni, Schistosomiasis mansoni, Sequence Homology, Small Interfering, Western},
pubstate = {published},
tppubtype = {article}
}
We have identified and characterized a Macrophage Migration Inhibitory Factor (MIF) family member in the Lophotrochozoan invertebrate, Biomphalaria glabrata, the snail intermediate host of the human blood fluke Schistosoma mansoni. In mammals, MIF is a widely expressed pleiotropic cytokine with potent pro-inflammatory properties that controls cell functions such as gene expression, proliferation or apoptosis. Here we show that the MIF protein from B. glabrata (BgMIF) is expressed in circulating immune defense cells (hemocytes) of the snail as well as in the B. glabrata embryonic (Bge) cell line that has hemocyte-like features. Recombinant BgMIF (rBgMIF) induced cell proliferation and inhibited NO-dependent p53-mediated apoptosis in Bge cells. Moreover, knock-down of BgMIF expression in Bge cells interfered with the in vitro encapsulation of S. mansoni sporocysts. Furthermore, the in vivo knock-down of BgMIF prevented the changes in circulating hemocyte populations that occur in response to an infection by S. mansoni miracidia and led to a significant increase in the parasite burden of the snails. These results provide the first functional evidence that a MIF ortholog is involved in an invertebrate immune response towards a parasitic infection and highlight the importance of cytokines in invertebrate-parasite interactions.
Paquette Nicholas, Broemer Meike, Aggarwal Kamna, Chen Li, Husson Marie, Ertürk-Hasdemir Deniz, Reichhart Jean-Marc, Meier Pascal, Silverman Neal
Caspase-mediated cleavage, IAP binding, and ubiquitination: linking three mechanisms crucial for Drosophila NF-kappaB signaling Article de journal
Dans: Mol. Cell, vol. 37, no. 2, p. 172–182, 2010, ISSN: 1097-4164.
Résumé | Liens | BibTeX | Étiquettes: Alleles, Amino Acid Motifs, Animals, Biological, Caspases, Inhibitor of Apoptosis Proteins, M3i, MAP Kinase Kinase Kinases, Models, NF-kappa B, reichhart, Sequence Alignment, Signal Transduction, Ubiquitin-Protein Ligases, Ubiquitination
@article{paquette_caspase-mediated_2010,
title = {Caspase-mediated cleavage, IAP binding, and ubiquitination: linking three mechanisms crucial for Drosophila NF-kappaB signaling},
author = {Nicholas Paquette and Meike Broemer and Kamna Aggarwal and Li Chen and Marie Husson and Deniz Ertürk-Hasdemir and Jean-Marc Reichhart and Pascal Meier and Neal Silverman},
doi = {10.1016/j.molcel.2009.12.036},
issn = {1097-4164},
year = {2010},
date = {2010-01-01},
journal = {Mol. Cell},
volume = {37},
number = {2},
pages = {172--182},
abstract = {Innate immune responses are critical for the immediate protection against microbial infection. In Drosophila, infection leads to the rapid and robust production of antimicrobial peptides through two NF-kappaB signaling pathways-IMD and Toll. The IMD pathway is triggered by DAP-type peptidoglycan, common to most Gram-negative bacteria. Signaling downstream from the peptidoglycan receptors is thought to involve K63 ubiquitination and caspase-mediated cleavage, but the molecular mechanisms remain obscure. We now show that PGN stimulation causes caspase-mediated cleavage of the imd protein, exposing a highly conserved IAP-binding motif (IBM) at its neo-N terminus. A functional IBM is required for the association of cleaved IMD with the ubiquitin E3-ligase DIAP2. Through its association with DIAP2, IMD is rapidly conjugated with K63-linked polyubiquitin chains. These results mechanistically connect caspase-mediated cleavage and K63 ubiquitination in immune-induced NF-kappaB signaling.},
keywords = {Alleles, Amino Acid Motifs, Animals, Biological, Caspases, Inhibitor of Apoptosis Proteins, M3i, MAP Kinase Kinase Kinases, Models, NF-kappa B, reichhart, Sequence Alignment, Signal Transduction, Ubiquitin-Protein Ligases, Ubiquitination},
pubstate = {published},
tppubtype = {article}
}
Innate immune responses are critical for the immediate protection against microbial infection. In Drosophila, infection leads to the rapid and robust production of antimicrobial peptides through two NF-kappaB signaling pathways-IMD and Toll. The IMD pathway is triggered by DAP-type peptidoglycan, common to most Gram-negative bacteria. Signaling downstream from the peptidoglycan receptors is thought to involve K63 ubiquitination and caspase-mediated cleavage, but the molecular mechanisms remain obscure. We now show that PGN stimulation causes caspase-mediated cleavage of the imd protein, exposing a highly conserved IAP-binding motif (IBM) at its neo-N terminus. A functional IBM is required for the association of cleaved IMD with the ubiquitin E3-ligase DIAP2. Through its association with DIAP2, IMD is rapidly conjugated with K63-linked polyubiquitin chains. These results mechanistically connect caspase-mediated cleavage and K63 ubiquitination in immune-induced NF-kappaB signaling.
2009
Shia Alice K H, Glittenberg Marcus, Thompson Gavin, Weber Alexander N R, Reichhart Jean-Marc, Ligoxygakis Petros
Toll-dependent antimicrobial responses in Drosophila larval fat body require Spätzle secreted by haemocytes Article de journal
Dans: J. Cell. Sci., vol. 122, no. Pt 24, p. 4505–4515, 2009, ISSN: 1477-9137.
Résumé | Liens | BibTeX | Étiquettes: Animals, Enterococcus faecalis, Escherichia coli, Fat Body, Hemocytes, Larva, M3i, reichhart, Toll-Like Receptors
@article{shia_toll-dependent_2009,
title = {Toll-dependent antimicrobial responses in Drosophila larval fat body require Spätzle secreted by haemocytes},
author = {Alice K H Shia and Marcus Glittenberg and Gavin Thompson and Alexander N R Weber and Jean-Marc Reichhart and Petros Ligoxygakis},
doi = {10.1242/jcs.049155},
issn = {1477-9137},
year = {2009},
date = {2009-12-01},
journal = {J. Cell. Sci.},
volume = {122},
number = {Pt 24},
pages = {4505--4515},
abstract = {In Drosophila, the humoral response characterised by the synthesis of antimicrobial peptides (AMPs) in the fat body (the equivalent of the mammalian liver) and the cellular response mediated by haemocytes (blood cells) engaged in phagocytosis represent two major reactions that counter pathogens. Although considerable analysis has permitted the elucidation of mechanisms pertaining to the two responses individually, the mechanism of their coordination has been unclear. To characterise the signals with which infection might be communicated between blood cells and fat body, we ablated circulating haemocytes and defined the parameters of AMP gene activation in larvae. We found that targeted ablation of blood cells influenced the levels of AMP gene expression in the fat body following both septic injury and oral infection. Expression of the AMP gene drosomycin (a Toll target) was blocked when expression of the Toll ligand Spätzle was knocked down in haemocytes. These results show that in larvae, integration of the two responses in a systemic reaction depend on the production of a cytokine (spz), a process that strongly parallels the mammalian immune response.},
keywords = {Animals, Enterococcus faecalis, Escherichia coli, Fat Body, Hemocytes, Larva, M3i, reichhart, Toll-Like Receptors},
pubstate = {published},
tppubtype = {article}
}
In Drosophila, the humoral response characterised by the synthesis of antimicrobial peptides (AMPs) in the fat body (the equivalent of the mammalian liver) and the cellular response mediated by haemocytes (blood cells) engaged in phagocytosis represent two major reactions that counter pathogens. Although considerable analysis has permitted the elucidation of mechanisms pertaining to the two responses individually, the mechanism of their coordination has been unclear. To characterise the signals with which infection might be communicated between blood cells and fat body, we ablated circulating haemocytes and defined the parameters of AMP gene activation in larvae. We found that targeted ablation of blood cells influenced the levels of AMP gene expression in the fat body following both septic injury and oral infection. Expression of the AMP gene drosomycin (a Toll target) was blocked when expression of the Toll ligand Spätzle was knocked down in haemocytes. These results show that in larvae, integration of the two responses in a systemic reaction depend on the production of a cytokine (spz), a process that strongly parallels the mammalian immune response.
Leclerc V, Caldelari I, Veresceaghina N, Reichhart J-M
Phagocytosis in Drosophila melanogaster Immune Response. Book Section
Dans: Phagocyte-pathogen Interactions, vol. 33, p. 513–521, DG Russel and S. Gordon, Whasington, DC, 2009.
BibTeX | Étiquettes: M3i, reichhart, ROMBY, Unité ARN
@incollection{leclerc_phagocytosis_2009,
title = {Phagocytosis in Drosophila melanogaster Immune Response.},
author = {V Leclerc and I Caldelari and N Veresceaghina and J-M Reichhart},
year = {2009},
date = {2009-01-01},
booktitle = {Phagocyte-pathogen Interactions},
volume = {33},
pages = {513--521},
publisher = {DG Russel and S. Gordon},
address = {Whasington, DC},
edition = {ASM Press},
keywords = {M3i, reichhart, ROMBY, Unité ARN},
pubstate = {published},
tppubtype = {incollection}
}
2008
Chamy L El, Leclerc V, Caldelari I, Reichhart J-M
Sensing of 'danger signals' and pathogen-associated molecular patterns defines binary signaling pathways 'upstream' of Toll Article de journal
Dans: Nat. Immunol., vol. 9, no. 10, p. 1165–1170, 2008, ISSN: 1529-2916.
Résumé | Liens | BibTeX | Étiquettes: Animals, Fungi, Genetically Modified, Gram-Positive Bacteria, Gram-Positive Bacterial Infections, In Situ Hybridization, M3i, Mycoses, Pattern Recognition, Peptide Hydrolases, Receptors, reichhart, ROMBY, Serine Endopeptidases, Signal Transduction, Toll-Like Receptors, Unité ARN
@article{el_chamy_sensing_2008,
title = {Sensing of 'danger signals' and pathogen-associated molecular patterns defines binary signaling pathways 'upstream' of Toll},
author = {L El Chamy and V Leclerc and I Caldelari and J-M Reichhart},
doi = {10.1038/ni.1643},
issn = {1529-2916},
year = {2008},
date = {2008-10-01},
journal = {Nat. Immunol.},
volume = {9},
number = {10},
pages = {1165--1170},
abstract = {In drosophila, molecular determinants from fungi and Gram-positive bacteria are detected by circulating pattern-recognition receptors. Published findings suggest that such pattern-recognition receptors activate as-yet-unidentified serine-protease cascades that culminate in the cleavage of Spätzle, the endogenous Toll receptor ligand, and trigger the immune response. We demonstrate here that the protease Grass defines a common activation cascade for the detection of fungi and Gram-positive bacteria mediated by pattern-recognition receptors. The serine protease Persephone, shown before to be specific for fungal detection in a cascade activated by secreted fungal proteases, was also required for the sensing of proteases elicited by bacteria in the hemolymph. Hence, Persephone defines a parallel proteolytic cascade activated by 'danger signals' such as abnormal proteolytic activities.},
keywords = {Animals, Fungi, Genetically Modified, Gram-Positive Bacteria, Gram-Positive Bacterial Infections, In Situ Hybridization, M3i, Mycoses, Pattern Recognition, Peptide Hydrolases, Receptors, reichhart, ROMBY, Serine Endopeptidases, Signal Transduction, Toll-Like Receptors, Unité ARN},
pubstate = {published},
tppubtype = {article}
}
In drosophila, molecular determinants from fungi and Gram-positive bacteria are detected by circulating pattern-recognition receptors. Published findings suggest that such pattern-recognition receptors activate as-yet-unidentified serine-protease cascades that culminate in the cleavage of Spätzle, the endogenous Toll receptor ligand, and trigger the immune response. We demonstrate here that the protease Grass defines a common activation cascade for the detection of fungi and Gram-positive bacteria mediated by pattern-recognition receptors. The serine protease Persephone, shown before to be specific for fungal detection in a cascade activated by secreted fungal proteases, was also required for the sensing of proteases elicited by bacteria in the hemolymph. Hence, Persephone defines a parallel proteolytic cascade activated by 'danger signals' such as abnormal proteolytic activities.
Goto Akira, Matsushita Kazufumi, Gesellchen Viola, Chamy Laure El, Kuttenkeuler David, Takeuchi Osamu, Hoffmann Jules A, Akira Shizuo, Boutros Michael, Reichhart Jean-Marc
Akirins are highly conserved nuclear proteins required for NF-kappaB-dependent gene expression in drosophila and mice Article de journal
Dans: Nat. Immunol., vol. 9, no. 1, p. 97–104, 2008, ISSN: 1529-2916.
Résumé | Liens | BibTeX | Étiquettes: Animals, Cell Line, Embryo, Fibroblasts, hoffmann, Humans, Immunity, Innate, Interleukin-1beta, M3i, Mammalian, Mice, NF-kappa B, Nuclear Proteins, Proteins, reichhart, Signal Transduction, Toll-Like Receptors, transgenic, Tumor Necrosis Factor-alpha
@article{goto_akirins_2008,
title = {Akirins are highly conserved nuclear proteins required for NF-kappaB-dependent gene expression in drosophila and mice},
author = {Akira Goto and Kazufumi Matsushita and Viola Gesellchen and Laure El Chamy and David Kuttenkeuler and Osamu Takeuchi and Jules A Hoffmann and Shizuo Akira and Michael Boutros and Jean-Marc Reichhart},
doi = {10.1038/ni1543},
issn = {1529-2916},
year = {2008},
date = {2008-01-01},
journal = {Nat. Immunol.},
volume = {9},
number = {1},
pages = {97--104},
abstract = {During a genome-wide screen with RNA-mediated interference, we isolated CG8580 as a gene involved in the innate immune response of Drosophila melanogaster. CG8580, which we called Akirin, encoded a protein that acted in parallel with the NF-kappaB transcription factor downstream of the Imd pathway and was required for defense against Gram-negative bacteria. Akirin is highly conserved, and the human genome contains two homologs, one of which was able to rescue the loss-of-function phenotype in drosophila cells. Akirins were strictly localized to the nucleus. Knockout of both Akirin homologs in mice showed that one had an essential function downstream of the Toll-like receptor, tumor necrosis factor and interleukin (IL)-1beta signaling pathways leading to the production of IL-6. Thus, Akirin is a conserved nuclear factor required for innate immune responses.},
keywords = {Animals, Cell Line, Embryo, Fibroblasts, hoffmann, Humans, Immunity, Innate, Interleukin-1beta, M3i, Mammalian, Mice, NF-kappa B, Nuclear Proteins, Proteins, reichhart, Signal Transduction, Toll-Like Receptors, transgenic, Tumor Necrosis Factor-alpha},
pubstate = {published},
tppubtype = {article}
}
During a genome-wide screen with RNA-mediated interference, we isolated CG8580 as a gene involved in the innate immune response of Drosophila melanogaster. CG8580, which we called Akirin, encoded a protein that acted in parallel with the NF-kappaB transcription factor downstream of the Imd pathway and was required for defense against Gram-negative bacteria. Akirin is highly conserved, and the human genome contains two homologs, one of which was able to rescue the loss-of-function phenotype in drosophila cells. Akirins were strictly localized to the nucleus. Knockout of both Akirin homologs in mice showed that one had an essential function downstream of the Toll-like receptor, tumor necrosis factor and interleukin (IL)-1beta signaling pathways leading to the production of IL-6. Thus, Akirin is a conserved nuclear factor required for innate immune responses.
2007
Gubb David, Robertson Andrew S, Troxler Laurent, Reichhart Jean-Marc
Drosophila Serpins: Regulatory Cascades in Innate Immunity and Morphogenesis Book Section
Dans: Molecular and Cellular Aspects of the Serpinopathies and Disorders in Serpin Activity, p. 207–227, Silverman GA and Lomas DA, London UK, 2007.
BibTeX | Étiquettes: bioinformatic, innate immunity, M3i, Morphogenesis, regulatory Cascades, reichhart, Serpins
@incollection{gubb_drosophila_2007,
title = {Drosophila Serpins: Regulatory Cascades in Innate Immunity and Morphogenesis},
author = {David Gubb and Andrew S Robertson and Laurent Troxler and Jean-Marc Reichhart},
year = {2007},
date = {2007-01-01},
booktitle = {Molecular and Cellular Aspects of the Serpinopathies and Disorders in Serpin Activity},
pages = {207--227},
publisher = {Silverman GA and Lomas DA},
address = {London UK},
edition = {World Scientific Pub.},
keywords = {bioinformatic, innate immunity, M3i, Morphogenesis, regulatory Cascades, reichhart, Serpins},
pubstate = {published},
tppubtype = {incollection}
}
2006
Gottar Marie, Gobert Vanessa, Matskevich Alexey A, Reichhart Jean-Marc, Wang Chengshu, Butt Tariq M, Belvin Marcia, Hoffmann Jules A, Ferrandon Dominique
Dual detection of fungal infections in Drosophila via recognition of glucans and sensing of virulence factors Article de journal
Dans: Cell, vol. 127, no. 7, p. 1425–1437, 2006, ISSN: 0092-8674.
Résumé | Liens | BibTeX | Étiquettes: Animals, Antibody Formation, Beauveria, Candida albicans, Carrier Proteins, Cellular, ferrandon, Glucans, hoffmann, Immunity, Immunological, M3i, Metarhizium, Models, Polysaccharides, reichhart, Serine Endopeptidases, Signal Transduction, Virulence Factors
@article{gottar_dual_2006,
title = {Dual detection of fungal infections in Drosophila via recognition of glucans and sensing of virulence factors},
author = {Marie Gottar and Vanessa Gobert and Alexey A Matskevich and Jean-Marc Reichhart and Chengshu Wang and Tariq M Butt and Marcia Belvin and Jules A Hoffmann and Dominique Ferrandon},
doi = {10.1016/j.cell.2006.10.046},
issn = {0092-8674},
year = {2006},
date = {2006-12-01},
journal = {Cell},
volume = {127},
number = {7},
pages = {1425--1437},
abstract = {The Drosophila immune system discriminates between various types of infections and activates appropriate signal transduction pathways to combat the invading microorganisms. The Toll pathway is required for the host response against fungal and most Gram-positive bacterial infections. The sensing of Gram-positive bacteria is mediated by the pattern recognition receptors PGRP-SA and GNBP1 that cooperate to detect the presence of infections in the host. Here, we report that GNBP3 is a pattern recognition receptor that is required for the detection of fungal cell wall components. Strikingly, we find that there is a second, parallel pathway acting jointly with GNBP3. The Drosophila Persephone protease activates the Toll pathway when proteolytically matured by the secreted fungal virulence factor PR1. Thus, the detection of fungal infections in Drosophila relies both on the recognition of invariant microbial patterns and on monitoring the effects of virulence factors on the host.},
keywords = {Animals, Antibody Formation, Beauveria, Candida albicans, Carrier Proteins, Cellular, ferrandon, Glucans, hoffmann, Immunity, Immunological, M3i, Metarhizium, Models, Polysaccharides, reichhart, Serine Endopeptidases, Signal Transduction, Virulence Factors},
pubstate = {published},
tppubtype = {article}
}
The Drosophila immune system discriminates between various types of infections and activates appropriate signal transduction pathways to combat the invading microorganisms. The Toll pathway is required for the host response against fungal and most Gram-positive bacterial infections. The sensing of Gram-positive bacteria is mediated by the pattern recognition receptors PGRP-SA and GNBP1 that cooperate to detect the presence of infections in the host. Here, we report that GNBP3 is a pattern recognition receptor that is required for the detection of fungal cell wall components. Strikingly, we find that there is a second, parallel pathway acting jointly with GNBP3. The Drosophila Persephone protease activates the Toll pathway when proteolytically matured by the secreted fungal virulence factor PR1. Thus, the detection of fungal infections in Drosophila relies both on the recognition of invariant microbial patterns and on monitoring the effects of virulence factors on the host.
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
Dans: EMBO Rep., vol. 7, no. 2, p. 231–235, 2006, ISSN: 1469-221X.
Résumé | Liens | BibTeX | Étiquettes: Animals, Bacterial Infections, Catechol Oxidase, Enzyme Activation, Enzyme Precursors, Gram-Negative Bacteria, Gram-Positive Bacteria, Hemolymph, hoffmann, Immunity, Innate, M3i, Mutation, reichhart, Survival Rate
@article{leclerc_prophenoloxidase_2006,
title = {Prophenoloxidase activation is not required for survival to microbial infections in Drosophila},
author = {Vincent Leclerc and Nadège Pelte and Laure El Chamy and Cosimo Martinelli and Petros Ligoxygakis and Jules A Hoffmann and Jean-Marc Reichhart},
doi = {10.1038/sj.embor.7400592},
issn = {1469-221X},
year = {2006},
date = {2006-02-01},
journal = {EMBO Rep.},
volume = {7},
number = {2},
pages = {231--235},
abstract = {The antimicrobial defence of Drosophila relies on cellular and humoral processes, of which the inducible synthesis of antimicrobial peptides has attracted interest in recent years. Another potential line of defence is the activation, by a proteolytic cascade, of phenoloxidase, which leads to the production of quinones and melanin. However, in spite of several publications on this subject, the contribution of phenoloxidase activation to resistance to infections has not been established under appropriate in vivo conditions. Here, we have isolated the first Drosophila mutant for a prophenoloxidase-activating enzyme (PAE1). In contrast to wild-type flies, PAE1 mutants fail to activate phenoloxidase in the haemolymph following microbial challenge. Surprisingly, we find that these mutants are as resistant to infections as wild-type flies, in the total absence of circulating phenoloxidase activity. This raises the question with regard to the precise function of phenoloxidase activation in defence, if any.},
keywords = {Animals, Bacterial Infections, Catechol Oxidase, Enzyme Activation, Enzyme Precursors, Gram-Negative Bacteria, Gram-Positive Bacteria, Hemolymph, hoffmann, Immunity, Innate, M3i, Mutation, reichhart, Survival Rate},
pubstate = {published},
tppubtype = {article}
}
The antimicrobial defence of Drosophila relies on cellular and humoral processes, of which the inducible synthesis of antimicrobial peptides has attracted interest in recent years. Another potential line of defence is the activation, by a proteolytic cascade, of phenoloxidase, which leads to the production of quinones and melanin. However, in spite of several publications on this subject, the contribution of phenoloxidase activation to resistance to infections has not been established under appropriate in vivo conditions. Here, we have isolated the first Drosophila mutant for a prophenoloxidase-activating enzyme (PAE1). In contrast to wild-type flies, PAE1 mutants fail to activate phenoloxidase in the haemolymph following microbial challenge. Surprisingly, we find that these mutants are as resistant to infections as wild-type flies, in the total absence of circulating phenoloxidase activity. This raises the question with regard to the precise function of phenoloxidase activation in defence, if any.
Pelte Nadège, Robertson Andrew S, Zou Zhen, Belorgey Didier, Dafforn Timothy R, Jiang Haobo, Lomas David, Reichhart Jean-Marc, Gubb David
Immune challenge induces N-terminal cleavage of the Drosophila serpin Necrotic Article de journal
Dans: Insect Biochem. Mol. Biol., vol. 36, no. 1, p. 37–46, 2006, ISSN: 0965-1748.
Résumé | Liens | BibTeX | Étiquettes: Animals, Gene Expression Regulation, M3i, Protein Conformation, reichhart, Serpins, Signal Transduction
@article{pelte_immune_2006,
title = {Immune challenge induces N-terminal cleavage of the Drosophila serpin Necrotic},
author = {Nadège Pelte and Andrew S Robertson and