I2CT

@article{Huang2023,

title = {A Toll pathway effector protects Drosophila specifically from distinct toxins secreted by a fungus or a bacterium},

author = {Jianqiong Huang and Yanyan Lou and Jiyong Liu and Philippe Bulet and Chuping Cai and Kaiyu Ma and Renjie Jiao and Jules A. Hoffmann and Samuel Liégeois and Zi Lia and Dominique Ferrandon},

editor = {Hugo Bellen, Baylor College of Medicine, Houston, TX},

url = {https://doi.org/10.1073/pnas.2205140120},

doi = {10.1073/pnas.2205140120},

year  = {2023},

date = {2023-03-14},

urldate = {2023-03-14},

journal = {PNAS},

volume = {120},

number = {12},

abstract = {Major immune response pathways control the expression of hundreds of genes that represent potential effectors of the immune response. The Drosophila Toll pathway is required in the host defenses against several Gram-positive bacterial infections as well as against fungal infections. The current paradigm is that peptides secreted in the hemolymph during the systemic immune response are either bona fide antimicrobial peptides or likely ones. The finding of a dual role for one Toll pathway effector in the resilience to both Enterococcus faecalis and Metarhizium robertsii infections underscores an original concept in insect innate immunity. Evolution can select effectors tailored to protect the host from the action of microbial toxins of prokaryotic or eukaryotic origin, independently of antibodies or detoxification pathways.},

keywords = {Baramicin A, Destruxin A, disease tolerance, enterocin O16, ferrandon, hoffmann, M3i, microbial toxins, resilience},

pubstate = {published},

tppubtype = {article}

}

@article{Goto2021,

title = {Verloren negatively regulates the expression of IMD pathway dependent antimicrobial peptides in Drosophila},

author = {Pragya Prakash and Arghyashree Roychowdhury-Sinha and Akira Goto},

url = {https://www.nature.com/articles/s41598-021-94973-0},

doi = {10.1038/s41598-021-94973-0},

year  = {2021},

date = {2021-07-30},

journal = {Scientific Reports},

volume = {11},

number = {15549},

abstract = {Drosophila immune deficiency (IMD) pathway is similar to the human tumor necrosis factor receptor (TNFR) signaling pathway and is preferentially activated by Gram-negative bacterial infection. Recent studies highlighted the importance of IMD pathway regulation as it is tightly controlled by numbers of negative regulators at multiple levels. Here, we report a new negative regulator of the IMD pathway, Verloren (Velo). Silencing of Velo led to constitutive expression of the IMD pathway dependent antimicrobial peptides (AMPs), and Escherichia coli stimulation further enhanced the AMP expression. Epistatic analysis indicated that Velo knock-down mediated AMP upregulation is dependent on the canonical members of the IMD pathway. The immune fluorescent study using overexpression constructs revealed that Velo resides both in the nucleus and cytoplasm, but the majority (~ 75%) is localized in the nucleus. We also observed from in vivo analysis that Velo knock-down flies exhibit significant upregulation of the AMP expression and reduced bacterial load. Survival experiments showed that Velo knock-down flies have a short lifespan and are susceptible to the infection of pathogenic Gram-negative bacteria, P. aeruginosa. Taken together, these data suggest that Velo is an additional new negative regulator of the IMD pathway, possibly acting in both the nucleus and cytoplasm.},

keywords = {bacteria, Biochemistry, DNA, Fungi, Gene Expression, gene regulation, Genetics, hoffmann, Immunochemistry, Immunology, infection, inflammation, Innate immune cells, innate immunity, M3i, microbiology, Molecular Biology, pathogens, RNA, RNAi, Signal Transduction, Transcription},

pubstate = {published},

tppubtype = {article}

}

@article{chen2021,

title = {A time course transcriptomic analysis of host and injected oncogenic cells reveals new aspects of Drosophila immune defenses},

author = {Di Chen and Arghyashree Roychowdhury-Sinha and Pragya Prakash and Xiao Lan and Wenmin Fan and Akira Goto and Jules A. Hoffmann},

url = {https://www.pnas.org/content/118/12/e2100825118},

doi = {https://doi.org/10.1073/pnas.2100825118},

year  = {2021},

date = {2021-03-23},

journal = {PNAS},

volume = {118},

number = {12},

abstract = {Oncogenic RasV12 cells [A. Simcox et al., PLoS Genet. 4, e1000142 (2008)] injected into adult males proliferated massively after a lag period of several days, and led to the demise of the flies after 2 to 3 wk. The injection induced an early massive transcriptomic response that, unexpectedly, included more than 100 genes encoding chemoreceptors of various families. The kinetics of induction and the identities of the induced genes differed markedly from the responses generated by injections of microbes. Subsequently, hundreds of genes were up-regulated, attesting to intense catabolic activities in the flies, active tracheogenesis, and cuticulogenesis, as well as stress and inflammation-type responses. At 11 d after the injections, GFP-positive oncogenic cells isolated from the host flies exhibited a markedly different transcriptomic profile from that of the host and distinct from that at the time of their injection, including in particular up-regulated expression of genes typical for cells engaged in the classical antimicrobial response of Drosophila.},

keywords = {cancer, chemoreceptor, Drosophila melanogaster, goto, hoffmann, innate immunity, M3i, RasV12},

pubstate = {published},

tppubtype = {article}

}

@article{goto2020,

title = {The Kinase IKKβ Regulates a STING-and NF-κB-Dependent Antiviral Response Pathway in Drosophila},

author = {Akira Goto and Kiyoshi Okado and Nelson Martins and Hua Cai and Vincent Barbier and Olivier Lamiable and Laurent Troxler and Estelle Santiago and Lauriane Kuhn and Donggi Paik and Neal Silverman and Andreas Holleufer and Rune Hartmann and Jiyong Liu and Tao Peng and Jules A Hoffmann and Carine Meignin and Laurent Daeffler and Jean-Luc Imler

},

url = {https://www-sciencedirect-com.insb.bib.cnrs.fr/science/article/pii/S107476131930528X},

doi = {10.1016/j.immuni.2019.12.009 },

year  = {2020},

date = {2020-01-14},

journal = {Immunity},

volume = {52},

number = {1},

pages = {200},

abstract = {Antiviral immunity inDrosophilainvolves RNA inter-ference and poorly characterized inducible re-sponses. Here, we showed that two components ofthe IMD pathway, the kinase dIKKband the tran-scription factor Relish, were required to controlinfection by two picorna-like viruses. We identifieda set of genes induced by viral infection and regu-lated by dIKKband Relish, which included an ortho-log of STING. We showed that dSTING participatedin the control of infection by picorna-like viruses,acting upstream of dIKKbto regulate expression ofNazo, an antiviral factor. Our data reveal an antiviralfunction for STING in an animal model devoid of inter-ferons and suggest an evolutionarily ancient role forthis molecule in antiviral immunity.},

keywords = {antiviral, Drosophila, hoffmann, imler, Kinase, M3i, meignin, STING},

pubstate = {published},

tppubtype = {article}

}

@article{Goto2018,

title = {The Kinase IKKβ Regulates a STING- and NF-κB-Dependent Antiviral Response Pathway in Drosophila},

author = {Akira Goto and Kiyoshi Okado and Nelson Martins and Hua Cai and Vincent Barbier and Olivier Lamiable and Laurent Troxler and Estelle Santiago and Lauriane Kuhn and Donggi Paik and Neal Silverman and Andreas Holleufer and Rune Hartmann and Jiyong Liu and Tao Peng and Jules A Hoffmann and Carine Meignin and Laurent Daeffler and Jean-Luc Imler},

editor = {Elsevier Inc.},

url = {https://doi.org/10.1016/j.immuni.2018.07.013},

doi = {j.immuni.2018.07.013},

year  = {2018},

date = {2018-08-21},

journal = {Immunity},

number = {49},

pages = {225-234},

abstract = {Antiviral immunity in Drosophila involves RNA interference and poorly characterized inducible responses. Here, we showed that two components of the IMD pathway, the kinase dIKKβ and the transcription factor Relish, were required to control infection by two picorna-like viruses. We identified a set of genes induced by viral infection and regulated by dIKKβ and Relish, which included an ortholog of STING. We showed that dSTING participated in the control of infection by picorna-like viruses, acting upstream of dIKKβ to regulate expression of Nazo, an antiviral factor. Our data reveal an antiviral function for STING in an animal model devoid of interferons and suggest an evolutionarily ancient role for this molecule in antiviral immunity.},

keywords = {hoffmann, imler, M3i, meignin, PPSE},

pubstate = {published},

tppubtype = {article}

}

@article{lamiable_cytokine_2016,

title = {Cytokine Diedel and a viral homologue suppress the IMD pathway in Drosophila},

author = {Olivier Lamiable and Christine Kellenberger and Cordula Kemp and Laurent Troxler and Nadège Pelte and Michael Boutros and Joao Trindade Marques and Laurent Daeffler and Jules A Hoffmann and Alain Roussel and Jean-Luc Imler},

url = {http://www.pnas.org/content/113/3/698.abstract},

doi = {10.1073/pnas.1516122113},

issn = {0027-8424, 1091-6490},

year  = {2016},

date = {2016-01-19},

urldate = {2016-01-07},

journal = {PNAS},

volume = {113},

number = {3},

pages = {698–703},

abstract = {Viruses are obligatory intracellular parasites that suffer strong evolutionary pressure from the host immune system. Rapidly evolving viral genomes can adapt to this pressure by acquiring genes that counteract host defense mechanisms. For example, many vertebrate DNA viruses have hijacked cellular genes encoding cytokines or cytokine receptors to disrupt host cell communication. Insect viruses express suppressors of RNA interference or apoptosis, highlighting the importance of these cell intrinsic antiviral mechanisms in invertebrates. Here, we report the identification and characterization of a family of proteins encoded by insect DNA viruses that are homologous to a 12-kDa circulating protein encoded by the virus-induced Drosophila gene diedel (die). We show that die mutant flies have shortened lifespan and succumb more rapidly than controls when infected with Sindbis virus. This reduced viability is associated with deregulated activation of the immune deficiency (IMD) pathway of host defense and can be rescued by mutations in the genes encoding the homolog of IKKγ or IMD itself. Our results reveal an endogenous pathway that is exploited by insect viruses to modulate NF-κB signaling and promote fly survival during the antiviral response.},

keywords = {antiviral immunity, bioinformatic, cytokine, Edin, hoffmann, imler, M3i, Sindbis Virus, virokine},

pubstate = {published},

tppubtype = {article}

}

@article{lamiable_analysis_2016,

title = {Analysis of the Contribution of Hemocytes and Autophagy to Drosophila Antiviral Immunity},

author = {Olivier Lamiable and Johan Arnold and Isaque Joao Silva da de Faria and Roenick Proveti Olmo and Francesco Bergami and Carine Meignin and Jules A Hoffmann and Joao Trindade Marques and Jean-Luc Imler},

url = {http://jvi.asm.org/content/90/11/5415},

doi = {10.1128/JVI.00238-16},

issn = {0022-538X, 1098-5514},

year  = {2016},

date = {2016-01-01},

urldate = {2016-06-05},

journal = {J. Virol.},

volume = {90},

number = {11},

pages = {5415--5426},

keywords = {antiviral immunity, Autophagy, Hemocytes, hoffmann, imler, M3i, meignin},

pubstate = {published},

tppubtype = {article}

}

@article{chtarbanova_drosophila_2014,

title = {Drosophila C virus systemic infection leads to intestinal obstruction},

author = {Stanislava Chtarbanova and Olivier Lamiable and Kwang-Zin Lee and Delphine Galiana and Laurent Troxler and Carine Meignin and Charles Hetru and Jules A Hoffmann and Laurent Daeffler and Jean-Luc Imler},

url = {http://jvi.asm.org/content/88/24/14057},

doi = {10.1128/JVI.02320-14},

issn = {1098-5514},

year  = {2014},

date = {2014-12-01},

journal = {Journal of Virology},

volume = {88},

number = {24},

pages = {14057--14069},

abstract = {Drosophila C virus (DCV) is a positive-sense RNA virus belonging to the Dicistroviridae family. This natural pathogen of the model organism Drosophila melanogaster is commonly used to investigate antiviral host defense in flies, which involves both RNA interference and inducible responses. Although lethality is used routinely as a readout for the efficiency of the antiviral immune response in these studies, virus-induced pathologies in flies still are poorly understood. Here, we characterize the pathogenesis associated with systemic DCV infection. Comparison of the transcriptome of flies infected with DCV or two other positive-sense RNA viruses, Flock House virus and Sindbis virus, reveals that DCV infection, unlike those of the other two viruses, represses the expression of a large number of genes. Several of these genes are expressed specifically in the midgut and also are repressed by starvation. We show that systemic DCV infection triggers a nutritional stress in Drosophila which results from intestinal obstruction with the accumulation of peritrophic matrix at the entry of the midgut and the accumulation of the food ingested in the crop, a blind muscular food storage organ. The related virus cricket paralysis virus (CrPV), which efficiently grows in Drosophila, does not trigger this pathology. We show that DCV, but not CrPV, infects the smooth muscles surrounding the crop, causing extensive cytopathology and strongly reducing the rate of contractions. We conclude that the pathogenesis associated with systemic DCV infection results from the tropism of the virus for an important organ within the foregut of dipteran insects, the crop. IMPORTANCE: DCV is one of the few identified natural viral pathogens affecting the model organism Drosophila melanogaster. As such, it is an important virus for the deciphering of host-virus interactions in insects. We characterize here the pathogenesis associated with DCV infection in flies and show that it results from the tropism of the virus for an essential but poorly characterized organ in the digestive tract, the crop. Our results may have relevance for other members of the Dicistroviridae, some of which are pathogenic to beneficial or pest insect species.},

keywords = {Animals, bioinformatic, Dicistroviridae, Female, Gastrointestinal Tract, Gene Expression Profiling, hoffmann, imler, Intestinal Obstruction, M3i, meignin, Muscle, Nodaviridae, Sindbis Virus, Smooth, Viral Tropism},

pubstate = {published},

tppubtype = {article}

}

@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}

}

@article{goto_chromatin_2014,

title = {The chromatin regulator DMAP1 modulates activity of the nuclear factor B (NF-B) transcription factor Relish in the Drosophila innate immune response},

author = {Akira Goto and Hidehiro Fukuyama and Jean-Luc Imler and Jules A Hoffmann},

doi = {10.1074/jbc.C114.553719},

issn = {1083-351X},

year  = {2014},

date = {2014-07-01},

journal = {The Journal of Biological Chemistry},

volume = {289},

number = {30},

pages = {20470--20476},

abstract = {The host defense of the model organism Drosophila is under the control of two major signaling cascades controlling transcription factors of the NF-B family, the Toll and the immune deficiency (IMD) pathways. The latter shares extensive similarities with the mammalian TNF-R pathway and was initially discovered for its role in anti-Gram-negative bacterial reactions. A previous interactome study from this laboratory reported that an unexpectedly large number of proteins are binding to the canonical components of the IMD pathway. Here, we focus on DNA methyltransferase-associated protein 1 (DMAP1), which this study identified as an interactant of Relish, a Drosophila transcription factor reminiscent of the mammalian p105 NF-B protein. We show that silencing of DMAP1 expression both in S2 cells and in flies results in a significant reduction of Escherichia coli-induced expression of antimicrobial peptides. Epistatic analysis indicates that DMAP1 acts in parallel or downstream of Relish. Co-immunoprecipitation experiments further reveal that, in addition to Relish, DMAP1 also interacts with Akirin and the Brahma-associated protein 55 kDa (BAP55). Taken together, these results reveal that DMAP1 is a novel nuclear modulator of the IMD pathway, possibly acting at the level of chromatin remodeling.},

keywords = {Animals, Cell Line, Chromatin Assembly and Disassembly, Epistasis, Escherichia coli, Escherichia coli Infections, Genetic, hoffmann, imler, Immunity, Innate, M3i, NF-kappa B, Repressor Proteins, Signal Transduction, Transcription Factors},

pubstate = {published},

tppubtype = {article}

}

@article{,

title = {RACK1 Controls IRES-Mediated Translation of Viruses.},

author = {K Majzoub and M L Hafirassou and C Meignin and A Goto and S Marzi and A Fedorova and Y Verdier and J Vinh and J A Hoffmann and F Martin and T F Baumert and C Schuster and JL Imler},

url = {http://www.ncbi.nlm.nih.gov/pubmed/25416947},

doi = {10.1016/j.cell.2014.10.041},

isbn = {25416947},

year  = {2014},

date = {2014-01-01},

journal = {Cell},

volume = {159},

number = {5},

pages = {1086-1095},

abstract = {Fighting viral infections is hampered by the scarcity of viral targets and their variability, resulting in development of resistance. Viruses depend on cellular molecules-which are attractive alternative targets-for their life cycle, provided that they are dispensable for normal cell functions. Using the model organism Drosophila melanogaster, we identify the ribosomal protein RACK1 as a cellular factor required for infection by internal ribosome entry site (IRES)-containing viruses. We further show that RACK1 is an essential determinant for hepatitis C virus translation and infection, indicating that its function is conserved for distantly related human and fly viruses. Inhibition of RACK1 does not affect Drosophila or human cell viability and proliferation, and RACK1-silenced adult flies are viable, indicating that this protein is not essential for general translation. Our findings demonstrate a specific function for RACK1 in selective mRNA translation and uncover a target for the development of broad antiviral intervention.},

keywords = {ERIANI, hoffmann, imler, M3i, meignin, ROMBY, Unité ARN},

pubstate = {published},

tppubtype = {article}

}

@article{fukuyama_landscape_2013,

title = {Landscape of protein-protein interactions in Drosophila immune deficiency signaling during bacterial challenge},

author = {Hidehiro Fukuyama and Yann Verdier and Yongsheng Guan and Chieko Makino-Okamura and Victoria Shilova and Xi Liu and Elie Maksoud and Jun Matsubayashi and Iman Haddad and Kerstin Spirohn and Kenichiro Ono and Charles Hetru and Jean Rossier and Trey Ideker and Michael Boutros and Joëlle Vinh and Jules A Hoffmann},

doi = {10.1073/pnas.1304380110},

issn = {1091-6490},

year  = {2013},

date = {2013-06-01},

journal = {Proc. Natl. Acad. Sci. U.S.A.},

volume = {110},

number = {26},

pages = {10717--10722},

abstract = {The Drosophila defense against pathogens largely relies on the activation of two signaling pathways: immune deficiency (IMD) and Toll. The IMD pathway is triggered mainly by Gram-negative bacteria, whereas the Toll pathway responds predominantly to Gram-positive bacteria and fungi. The activation of these pathways leads to the rapid induction of numerous NF-κB-induced immune response genes, including antimicrobial peptide genes. The IMD pathway shows significant similarities with the TNF receptor pathway. Recent evidence indicates that the IMD pathway is also activated in response to various noninfectious stimuli (i.e., inflammatory-like reactions). To gain a better understanding of the molecular machinery underlying the pleiotropic functions of this pathway, we first performed a comprehensive proteomics analysis to identify the proteins interacting with the 11 canonical members of the pathway initially identified by genetic studies. We identified 369 interacting proteins (corresponding to 291 genes) in heat-killed Escherichia coli-stimulated Drosophila S2 cells, 92% of which have human orthologs. A comparative analysis of gene ontology from fly or human gene annotation databases points to four significant common categories: (i) the NuA4, nucleosome acetyltransferase of H4, histone acetyltransferase complex, (ii) the switching defective/sucrose nonfermenting-type chromatin remodeling complex, (iii) transcription coactivator activity, and (iv) translation factor activity. Here we demonstrate that sumoylation of the IκB kinase homolog immune response-deficient 5 plays an important role in the induction of antimicrobial peptide genes through a highly conserved sumoylation consensus site during bacterial challenge. Taken together, the proteomics data presented here provide a unique avenue for a comparative functional analysis of proteins involved in innate immune reactions in flies and mammals.},

keywords = {Amino Acid, Animals, Chromatin Assembly and Disassembly, Escherichia coli, functional proteomics, Genes, Genetically Modified, Histone Acetyltransferases, hoffmann, Host-Pathogen Interactions, Humans, IMD interactome, Insect, M3i, Models, Molecular, Protein Interaction Maps, Sequence Homology, Signal Transduction, small ubiquitin-like modifier},

pubstate = {published},

tppubtype = {article}

}

@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}

}

@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}

}

@article{liu_drosophila_2012,

title = {Drosophila EYA regulates the immune response against DNA through an evolutionarily conserved threonine phosphatase motif},

author = {Xi Liu and Teruyuki Sano and Yongsheng Guan and Shigekazu Nagata and Jules A Hoffmann and Hidehiro Fukuyama},

doi = {10.1371/journal.pone.0042725},

issn = {1932-6203},

year  = {2012},

date = {2012-01-01},

journal = {PLoS ONE},

volume = {7},

number = {8},

pages = {e42725},

abstract = {Innate immune responses against DNA are essential to counter both pathogen infections and tissue damages. Mammalian EYAs were recently shown to play a role in regulating the innate immune responses against DNA. Here, we demonstrate that the unique Drosophila eya gene is also involved in the response specific to DNA. Haploinsufficiency of eya in mutants deficient for lysosomal DNase activity (DNaseII) reduces antimicrobial peptide gene expression, a hallmark for immune responses in flies. Like the mammalian orthologues, Drosophila EYA features a N-terminal threonine and C-terminal tyrosine phosphatase domain. Through the generation of a series of mutant EYA fly strains, we show that the threonine phosphatase domain, but not the tyrosine phosphatase domain, is responsible for the innate immune response against DNA. A similar role for the threonine phosphatase domain in mammalian EYA4 had been surmised on the basis of in vitro studies. Furthermore EYA associates with IKKβ and full-length RELISH, and the induction of the IMD pathway-dependent antimicrobial peptide gene is independent of SO. Our data provide the first in vivo demonstration for the immune function of EYA and point to their conserved immune function in response to endogenous DNA, throughout evolution.},

keywords = {Amino Acid, Animals, Blotting, Conserved Sequence, Endodeoxyribonucleases, Eye Proteins, hoffmann, Immunoprecipitation, M3i, Phosphoprotein Phosphatases, Sequence Homology, Transcription Factors, Western},

pubstate = {published},

tppubtype = {article}

}

@article{eleftherianos_atp-sensitive_2011,

title = {ATP-sensitive potassium channel (K(ATP))-dependent regulation of cardiotropic viral infections},

author = {Ioannis Eleftherianos and Sungyong Won and Stanislava Chtarbanova and Barbara Squiban and Karen Ocorr and Rolf Bodmer and Bruce Beutler and Jules A Hoffmann and Jean-Luc Imler},

doi = {10.1073/pnas.1108926108},

issn = {1091-6490},

year  = {2011},

date = {2011-07-01},

journal = {Proceedings of the National Academy of Sciences of the United States of America},

volume = {108},

number = {29},

pages = {12024--12029},

abstract = {The effects of the cellular environment on innate immunity remain poorly characterized. Here, we show that in Drosophila ATP-sensitive potassium channels (K(ATP)) mediate resistance to a cardiotropic RNA virus, Flock House virus (FHV). FHV viral load in the heart rapidly increases in K(ATP) mutant flies, leading to increased viremia and accelerated death. The effect of K(ATP) channels is dependent on the RNA interference genes Dcr-2, AGO2, and r2d2, indicating that an activity associated with this potassium channel participates in this antiviral pathway in Drosophila. Flies treated with the K(ATP) agonist drug pinacidil are protected against FHV infection, thus demonstrating the importance of this regulation of innate immunity by the cellular environment in the heart. In mice, the Coxsackievirus B3 replicates to higher titers in the hearts of mayday mutant animals, which are deficient in the Kir6.1 subunit of K(ATP) channels, than in controls. Together, our data suggest that K(ATP) channel deregulation can have a critical impact on innate antiviral immunity in the heart.},

keywords = {Animals, Heart, HeLa Cells, hoffmann, Humans, imler, Immunity, Immunoblotting, Inbred C57BL, Innate, KATP Channels, M3i, Mice, Nodaviridae, Pinacidil, Reverse Transcriptase Polymerase Chain Reaction, RNA Interference, Tolbutamide, Viral Load, Viremia},

pubstate = {published},

tppubtype = {article}

}

@article{hetru_nf-kappab_2009,

title = {NF-kappaB in the immune response of Drosophila},

author = {Charles Hetru and Jules A Hoffmann},

doi = {10.1101/cshperspect.a000232},

issn = {1943-0264},

year  = {2009},

date = {2009-12-01},

journal = {Cold Spring Harb Perspect Biol},

volume = {1},

number = {6},

pages = {a000232},

abstract = {The nuclear factor kappaB (NF-kappaB) pathways play a major role in Drosophila host defense. Two recognition and signaling cascades control this immune response. The Toll pathway is activated by Gram-positive bacteria and by fungi, whereas the immune deficiency (Imd) pathway responds to Gram-negative bacterial infection. The basic mechanisms of recognition of these various types of microbial infections by the adult fly are now globally understood. Even though some elements are missing in the intracellular pathways, numerous proteins and interactions have been identified. In this article, we present a general picture of the immune functions of NF-kappaB in Drosophila with all the partners involved in recognition and in the signaling cascades.},

keywords = {Animals, bacteria, Fungi, Gene Expression Regulation, hoffmann, M3i, NF-kappa B},

pubstate = {published},

tppubtype = {article}

}

@article{mishima_n-terminal_2009,

title = {The N-terminal domain of Drosophila Gram-negative binding protein 3 (GNBP3) defines a novel family of fungal pattern recognition receptors},

author = {Yumiko Mishima and Jessica Quintin and Vishukumar Aimanianda and Christine Kellenberger and Franck Coste and Cecile Clavaud and Charles Hetru and Jules A Hoffmann and Jean-Paul Latgé and Dominique Ferrandon and Alain Roussel},

doi = {10.1074/jbc.M109.034587},

issn = {1083-351X},

year  = {2009},

date = {2009-10-01},

journal = {J. Biol. Chem.},

volume = {284},

number = {42},

pages = {28687--28697},

abstract = {Gram-negative binding protein 3 (GNBP3), a pattern recognition receptor that circulates in the hemolymph of Drosophila, is responsible for sensing fungal infection and triggering Toll pathway activation. Here, we report that GNBP3 N-terminal domain binds to fungi upon identifying long chains of beta-1,3-glucans in the fungal cell wall as a major ligand. Interestingly, this domain fails to interact strongly with short oligosaccharides. The crystal structure of GNBP3-Nter reveals an immunoglobulin-like fold in which the glucan binding site is masked by a loop that is highly conserved among glucan-binding proteins identified in several insect orders. Structure-based mutagenesis experiments reveal an essential role for this occluding loop in discriminating between short and long polysaccharides. The displacement of the occluding loop is necessary for binding and could explain the specificity of the interaction with long chain structured polysaccharides. This represents a novel mechanism for beta-glucan recognition.},

keywords = {Animals, beta-Glucans, Bombyx, Carrier Proteins, Crystallography, ferrandon, Fungal Proteins, Hemolymph, hoffmann, ligands, M3i, Molecular Conformation, Mutagenesis, Polysaccharides, Protein Structure, Secondary, Tertiary, X-Ray},

pubstate = {published},

tppubtype = {article}

}