M3i

@article{nokey,

title = {The virus-induced cyclic dinucleotide 2'3'-c-di-GMP mediates STING-dependent antiviral immunity in Drosophila},

author = {Cai H and Li L and Slavik KM and Huang J and Yin T and Ai X and Hédelin L and Haas G and Xiang Z and Yang Y and Li X and Chen Y and Wei Z and Deng H and Chen D and Jiao R and Martins N and Meignin C and Kranzusch PJ and Imler JL},

editor = {Elsevier Inc. },

url = {https://pubmed.ncbi.nlm.nih.gov/37659413/},

doi = {10.1016/j.immuni.2023.08.006 },

year  = {2023},

date = {2023-09-12},

urldate = {2023-09-12},

journal = {Immunity},

volume = {56},

issue = {9},

pages = {1991-2005},

abstract = {In mammals, the enzyme cGAS senses the presence of cytosolic DNA and synthesizes the cyclic dinucleotide (CDN) 2'3'-cGAMP, which triggers STING-dependent immunity. In Drosophila melanogaster, two cGAS-like receptors (cGLRs) produce 3'2'-cGAMP and 2'3'-cGAMP to activate STING. We explored CDN-mediated immunity in 14 Drosophila species covering 50 million years of evolution and found that 2'3'-cGAMP and 3'2'-cGAMP failed to control infection by Drosophila C virus in D. serrata and two other species. We discovered diverse CDNs produced in a cGLR-dependent manner in response to viral infection in D. melanogaster, including 2'3'-c-di-GMP. This CDN was a more potent STING agonist than cGAMP in D. melanogaster and it also activated a strong antiviral transcriptional response in D. serrata. Our results shed light on the evolution of cGLRs in flies and provide a basis for understanding the function and regulation of this emerging family of pattern recognition receptors in animal innate immunity. },

keywords = {c-di-GMP, cGAMP, cGAS, cGLR, cyclic dinucleotide, Drosophila, Evolution, Hua, imler, M3i, meignin, pattern recognition receptor, STING, virus},

pubstate = {published},

tppubtype = {article}

}

@article{IGNELL2023,

title = {A mosquito-specific antennal protein is critical for the attraction to human odor in the malaria vector Anopheles gambiae},

author = {Julien PELLETIER AND Mengistu DAWIT AND Majid GHANINIA AND Eric MAROIS AND Rickard IGNELL},

editor = { },

url = {https://doi.org/10.1016/j.ibmb.2023.103988},

doi = {j.ibmb.2023.103988},

year  = {2023},

date = {2023-07-11},

urldate = {2023-07-11},

journal = {Insect Biochemistry and Molecular Biology},

volume = {159},

issue = {August 2023},

abstract = {Mosquitoes rely mainly on the sense of smell to decipher their environment and locate suitable food sources, hosts for blood feeding and oviposition sites. The molecular bases of olfaction involve multigenic families of olfactory proteins that have evolved to interact with a narrow set of odorants that are critical for survival. Understanding the complex interplay between diversified repertoires of olfactory proteins and ecologically-relevant odorant signals, which elicit important behaviors, is fundamental for the design of novel control strategies targeting the sense of smell of disease vector mosquitoes. Previously, large multigene families of odorant receptor and ionotropic receptor proteins, as well as a subset of odorant-binding proteins have been shown to mediate the selectivity and sensitivity of the mosquito olfactory system. In this study, we identify a mosquito-specific antennal protein (MSAP) gene as a novel molecular actor of odorant reception. MSAP is highly conserved across mosquito species and is transcribed at an extremely high level in female antennae. In order to understand its role in the mosquito olfactory system, we generated knockout mutant lines in Anopheles gambiae, and performed comparative analysis of behavioral and physiological responses to human-associated odorants. We found that MSAP promotes female mosquito attraction to human odor and enhances the sensitivity of the antennae to a variety of odorants. These findings suggest that MSAP is an important component of the mosquito olfactory system, which until now has gone completely unnoticed.},

keywords = {antenna, chemoreceptor, M3i, marois, mosquitoes, olfaction},

pubstate = {published},

tppubtype = {article}

}

@article{deFaria2023,

title = {Protocol for the analysis of double-stranded RNAs in virus-infected insect cells using anti-dsRNA antibodies},

author = {Isaque J.S. de Faria and Jean-Luc Imler and João T. Marques},

url = {https://doi.org/10.1016/j.xpro.2022.102033},

doi = {10.1016/j.xpro.2022.102033},

year  = {2023},

date = {2023-03-17},

urldate = {2023-03-17},

journal = {STAR Protocols},

volume = {4},

issue = {1},

abstract = {Characterization of double-stranded (ds)RNAs is relevant to the understanding of viral replication and immune sensing. Here, we provide a protocol describing the use of anti-dsRNA antibodies for immunofluorescence and immunoblotting in virus-infected insect cells, which can also be applied to tissues and other organisms. We describe the procedures to prepare insect cells for viral infection, followed by RNA extraction and in vitro production of synthetic dsRNA controls. We then detail the steps for dsRNA detection by immunoblotting and immunofluorescence. For complete details on the use and execution of this protocol, please refer to de Faria et al. (2022).1},

keywords = {antibody, cell bioloby, Immunology, M3i, Marques, microbiology, Microscopy, Molecular Biology},

pubstate = {published},

tppubtype = {article}

}

@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{Klug2023,

title = {The salivary protein Saglin facilitates efficient midgut colonization of Anopheles mosquitoes by malaria parasites},

author = {Dennis Klug and Amandine Gautier and Eric Calvo and Eric Marois and Stéphanie A. Blandin},

url = {https://doi.org/10.1371/journal.ppat.1010538},

doi = {10.1371/journal.ppat.1010538},

year  = {2023},

date = {2023-03-02},

urldate = {2023-03-02},

booktitle = {Plos Pathogens},

journal = {Plos Pathogens},

volume = {19},

number = {3},

issue = {3},

abstract = {Female mosquitoes rely on blood feeding to acquire sufficient nutrients for egg development. Because of the importance of this process mosquitoes evolved salivary proteins with a broad range of functions acting as blood thinners, anti-coagulants and immunosuppressants. The effect of these proteins on the blood at the bite site directly influences the size of the blood bolus a female takes up in a given time frame. Both, time of feeding and bolus size, are important parameters for fecundity and survival. Recent studies have shown that a significant proportion of salivated proteins is re-ingested during feeding and becomes part of the blood meal. Here we investigated the salivary protein Saglin which has been previously suggested as putative receptor mediating malaria parasite entry into the salivary gland. By engineering a loss-of-function mutant in An. coluzzi we could show that the absence of Saglin impairs the development of parasite stages in the blood meal of the rodent malaria parasite P. berghei and the human malaria parasite P. falciparum lowering the parasite burden of subsequent stages and preventing efficient transmission at low infection densities. Furthermore, we could show that Saglin is present in the blood meal after feeding possibly indicating a previously overlooked parasite-vector interaction.},

keywords = {blandin, BLOOD, M3i, malarial parasites, marois, mosquitoes, Oocysts, Parasitic Diseases, Plasmodium, salivary glands, sporozoites},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36322050,

title = {The Toll pathway mediates Drosophila resilience to Aspergillus mycotoxins through specific Bomanins},

author = {Rui Xu and Yanyan Lou and Antonin Tidu and Philippe Bulet and Thorsten Heinekamp and Franck Martin and Axel Brakhage and Zi Li and Samuel Liégeois and Dominique Ferrandon},

url = {https://pubmed.ncbi.nlm.nih.gov/36322050/},

doi = {10.15252/embr.202256036},

issn = {1469-3178},

year  = {2022},

date = {2022-11-01},

urldate = {2022-11-01},

journal = {EMBO Rep},

pages = {e56036},

abstract = {Host defense against infections encompasses both resistance, which targets microorganisms for neutralization or elimination, and resilience/disease tolerance, which allows the host to withstand/tolerate pathogens and repair damages. In Drosophila, the Toll signaling pathway is thought to mediate resistance against fungal infections by regulating the secretion of antimicrobial peptides, potentially including Bomanins. We find that Aspergillus fumigatus kills Drosophila Toll pathway mutants without invasion because its dissemination is blocked by melanization, suggesting a role for Toll in host defense distinct from resistance. We report that mutants affecting the Toll pathway or the 55C Bomanin locus are susceptible to the injection of two Aspergillus mycotoxins, restrictocin and verruculogen. The vulnerability of 55C deletion mutants to these mycotoxins is rescued by the overexpression of Bomanins specific to each challenge. Mechanistically, flies in which BomS6 is expressed in the nervous system exhibit an enhanced recovery from the tremors induced by injected verruculogen and display improved survival. Thus, innate immunity also protects the host against the action of microbial toxins through secreted peptides and thereby increases its resilience to infection.},

keywords = {ERIANI, ferrandon, M3i, MARTIN, Unité ARN},

pubstate = {published},

tppubtype = {article}

}

@article{dedaMarques2022,

title = {Invading viral DNA triggers dsRNA synthesis by RNA polymerase II to activate antiviral RNA interference in Drosophila},

author = {Isaque J.S. de Faria and Eric R.G.R. Aguiar and Roenick P. Olmo and Juliana Alves da Silva and Laurent Daeffler and Richard W. Carthew and Jean-Luc Imler and Joao T. Marques},

doi = {10.1016/j.celrep.2022.110976},

year  = {2022},

date = {2022-06-21},

urldate = {2022-06-21},

journal = {Cell Reports},

volume = {39},

pages = {110976},

abstract = {dsRNA sensing triggers antiviral responses against RNA and DNA viruses in diverse eukaryotes. In Drosophila, Invertebrate iridescent virus 6 (IIV-6), a large DNA virus, triggers production of small interfering RNAs (siRNAs) by the dsRNA sensor Dicer-2. Here, we show that host RNA polymerase II (RNAPII) bidirec- tionally transcribes specific AT-rich regions of the IIV-6 DNA genome to generate dsRNA. Both replicative and naked IIV-6 genomes trigger production of dsRNA in Drosophila cells, implying direct sensing of invading DNA. Loquacious-PD, a Dicer-2 co-factor essential for the biogenesis of endogenous siRNAs, is dispensable for processing of IIV-6-derived dsRNAs, which suggests that they are distinct. Consistent with this finding, inhibition of the RNAPII co-factor P-TEFb affects the synthesis of endogenous, but not virus-derived, dsRNA. Altogether, our results suggest that a non-canonical RNAPII complex recognizes invading viral DNA to synthesize virus-derived dsRNA, which activates the antiviral siRNA pathway in Drosophila.},

keywords = {antiviral, Drosophila, dsRNA, imler, M3i, Marques, protocol, RNA Interference},

pubstate = {published},

tppubtype = {article}

}

@article{Imler2022,

title = {cGAS-like receptor-mediated immunity: the insect perspective},

author = {H Cai and C Meignin and JL Imler},

doi = {10.1016/j.coi.2022.01.005},

year  = {2022},

date = {2022-02-08},

urldate = {2022-02-08},

journal = {Current Opinion in Immunology},

volume = {74},

pages = {183-189},

abstract = {The cGAS-STING pathway plays a central role in the detection of DNA in the cytosol of mammalian cells and activation of immunity. Although the early evolutionary origin of this pathway in animals has been noted, its ancestral functions have remained elusive so far. We review here new findings in invertebrates establishing a role in sensing and signaling infection, triggering potent transcriptional responses, in addition to autophagy. Results from flies and moths/butterflies points to the importance of STING signaling in antiviral immunity in insects. The recent characterization of cGAS-like receptors in Drosophila reveals the plasticity of this family of pattern-recognition receptors, able to accommodate ligands different from DNA and to produce cyclic dinucleotides beyond 2′3′-cGAMP.},

keywords = {imler, M3i, meignin},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34853303,

title = {Cross-species analysis of viral nucleic acid interacting proteins identifies TAOKs as innate immune regulators},

author = {Friederike L Pennemann and Assel Mussabekova and Christian Urban and Alexey Stukalov and Line Lykke Andersen and Vincent Grass and Teresa Maria Lavacca and Cathleen Holze and Lila Oubraham and Yasmine Benamrouche and Enrico Girardi and Rasha E Boulos and Rune Hartmann and Giulio Superti-Furga and Matthias Habjan and Jean-Luc Imler and Carine Meignin and Andreas Pichlmair},

doi = {10.1038/s41467-021-27192-w},

issn = {2041-1723},

year  = {2021},

date = {2021-12-01},

urldate = {2021-12-01},

journal = {Nat Commun},

volume = {12},

number = {1},

pages = {7009},

abstract = {The cell intrinsic antiviral response of multicellular organisms developed over millions of years and critically relies on the ability to sense and eliminate viral nucleic acids. Here we use an affinity proteomics approach in evolutionary distant species (human, mouse and fly) to identify proteins that are conserved in their ability to associate with diverse viral nucleic acids. This approach shows a core of orthologous proteins targeting viral genetic material and species-specific interactions. Functional characterization of the influence of 181 candidates on replication of 6 distinct viruses in human cells and flies identifies 128 nucleic acid binding proteins with an impact on virus growth. We identify the family of TAO kinases (TAOK1, -2 and -3) as dsRNA-interacting antiviral proteins and show their requirement for type-I interferon induction. Depletion of TAO kinases in mammals or flies leads to an impaired response to virus infection characterized by a reduced induction of interferon stimulated genes in mammals and impaired expression of srg1 and diedel in flies. Overall, our study shows a larger set of proteins able to mediate the interaction between viral genetic material and host factors than anticipated so far, attesting to the ancestral roots of innate immunity and to the lineage-specific pressures exerted by viruses.},

keywords = {antiviral innate immunity, imler, M3i, meignin},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34452932,

title = {Protein Phosphatase 4 Negatively Regulates the Immune Deficiency-NF-κB Pathway during the  Immune Response},

author = {Layale Salem Wehbe and Dana Barakat and Adrian Acker and Rita El Khoury and Jean-Marc Reichhart and Nicolas Matt and Laure El Chamy},

doi = {10.4049/jimmunol.1901497},

issn = {1550-6606},

year  = {2021},

date = {2021-08-27},

urldate = {2021-08-27},

journal = {J Immunol},

volume = {207},

number = {6},

pages = {1616--1626},

abstract = {The evolutionarily conserved immune deficiency (IMD) signaling pathway shields  against bacterial infections. It regulates the expression of antimicrobial peptides encoding genes through the activation of the NF-κB transcription factor Relish. Tight regulation of the signaling cascade ensures a balanced immune response, which is otherwise highly harmful. Several phosphorylation events mediate intracellular progression of the IMD pathway. However, signal termination by dephosphorylation remains largely elusive. Here, we identify the highly conserved protein phosphatase 4 (PP4) complex as a bona fide negative regulator of the IMD pathway. RNA interference-mediated gene silencing of , , and  which encode the catalytic and regulatory subunits of the phosphatase complex, respectively, caused a marked upregulation of bacterial-induced antimicrobial peptide gene expression in both  S2 cells and adult flies. Deregulated IMD signaling is associated with reduced lifespan of -deficient flies in the absence of any infection. In contrast, flies overexpressing this phosphatase are highly sensitive to bacterial infections. Altogether, our results highlight an evolutionarily conserved function of PP4c in the regulation of NF-κB signaling from  to mammals.},

keywords = {Drosophila, IKK complex, IMD, immune response, M3i, matt, NF-κB, PP4 complex},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34191026,

title = {Monitoring Insect Transposable Elements in Large Double-Stranded DNA Viruses Reveals Host-to-Virus and Virus-to-Virus Transposition},

author = {Vincent Loiseau and Jean Peccoud and Clémence Bouzar and Sandra Guillier and Jiangbin Fan and Gianpiero Gueli Alletti and Carine Meignin and Elisabeth A Herniou and Brian A Federici and Jörg T Wennmann and Johannes A Jehle and Richard Cordaux and Clément Gilbert},

doi = {10.1093/molbev/msab198},

issn = {1537-1719},

year  = {2021},

date = {2021-08-01},

urldate = {2021-08-01},

journal = {Mol Biol Evol},

volume = {38},

number = {9},

pages = {3512--3530},

abstract = {The mechanisms by which transposable elements (TEs) can be horizontally transferred between animals are unknown, but viruses are possible candidate vectors. Here, we surveyed the presence of host-derived TEs in viral genomes in 35 deep sequencing data sets produced from 11 host-virus systems, encompassing nine arthropod host species (five lepidopterans, two dipterans, and two crustaceans) and six different double-stranded (ds) DNA viruses (four baculoviruses and two iridoviruses). We found evidence of viral-borne TEs in 14 data sets, with frequencies of viral genomes carrying a TE ranging from 0.01% to 26.33% for baculoviruses and from 0.45% to 7.36% for iridoviruses. The analysis of viral populations separated by a single replication cycle revealed that viral-borne TEs originating from an initial host species can be retrieved after viral replication in another host species, sometimes at higher frequencies. Furthermore, we detected a strong increase in the number of integrations in a viral population for a TE absent from the hosts' genomes, indicating that this TE has undergone intense transposition within the viral population. Finally, we provide evidence that many TEs found integrated in viral genomes (15/41) have been horizontally transferred in insects. Altogether, our results indicate that multiple large dsDNA viruses have the capacity to shuttle TEs in insects and they underline the potential of viruses to act as vectors of horizontal transfer of TEs. Furthermore, the finding that TEs can transpose between viral genomes of a viral species sets viruses as possible new niches in which TEs can persist and evolve.},

keywords = {M3i, meignin},

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{Hartmann2021,

title = {Two cGAS-like receptors induce antiviral immunity in Drosophila},

author = {Andreas Holleufer AND Kasper Grønbjerg Winther AND Hans Henrik Gad AND Xianlong Ai AND Yuqiang Chen AND Lihua Li AND Ziming Wei AND Huimin Deng AND Jiyong Liu AND Ninna Ahlmann Frederiksen AND Bine Simonsen AND Line Lykke Andersen AND Karin Kleigrewe AND Louise Dalskov AND Andreas Pichlmair AND Hua Cai AND Jean-Luc Imler AND Rune Hartmann},

editor = {Nature Publishing Group},

doi = {https://doi.org/10.1038/s41586-021-03800-z},

year  = {2021},

date = {2021-07-14},

journal = {Nature},

volume = {597},

pages = {114-118},

abstract = {In mammals, cyclic GMP-AMP (cGAMP) synthase (cGAS) produces the cyclic dinucleotide (CDN) 2'3'-cGAMP in response to cytosolic DNA and this triggers an antiviral immune response. cGAS belongs to a large family of cGAS/DncV-like nucleotidyltransferases, present in both prokaryotes1 and eukaryotes2–5. In bacteria, these enzymes synthesize a range of cyclic oligonucleotide and have recently emerged as important regulators of phage infections6–8. Here, we identify two novel cGAS-like receptors (cGLRs) in the insect Drosophila melanogaster. We show that cGLR1 and cGLR2 activate Sting and NF-κB dependent antiviral immunity in response to infection with RNA or DNA viruses. cGLR1 is activated by dsRNA to produce the novel CDN 3'2'-cGAMP whereas cGLR2 produces a combination of 2'3'-cGAMP and 3'2' cGAMP in response to a yet unidentified stimulus. Our data establish cGAS as the founding member of a family of receptors sensing different types of nucleic acids and triggering immunity through production of CDNs beyond 2'3'-cGAMP.},

keywords = {antiviral immunity, cGAS-like receptors, Drosophila, imler, M3i},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34261127,

title = {cGAS-like receptors sense RNA and control 3'2'-cGAMP signalling in Drosophila},

author = {Kailey M Slavik and Benjamin R Morehouse and Adelyn E Ragucci and Wen Zhou and Xianlong Ai and Yuqiang Chen and Lihua Li and Ziming Wei and Heike Bähre and Martin König and Roland Seifert and Amy S Y Lee and Hua Cai and Jean-Luc Imler and Philip J Kranzusch},

doi = {10.1038/s41586-021-03743-5},

issn = {1476-4687},

year  = {2021},

date = {2021-07-14},

journal = {Nature},

volume = {597},

number = {7874},

pages = {109--113},

abstract = {Cyclic GMP-AMP synthase (cGAS) is a cytosolic DNA sensor that produces the second messenger cG[2'-5']pA[3'-5']p (2'3'-cGAMP) and controls activation of innate immunity in mammalian cells. Animal genomes typically encode multiple proteins with predicted homology to cGAS, but the function of these uncharacterized enzymes is unknown. Here we show that cGAS-like receptors (cGLRs) are innate immune sensors that are capable of recognizing divergent molecular patterns and catalysing synthesis of distinct nucleotide second messenger signals. Crystal structures of human and insect cGLRs reveal a nucleotidyltransferase signalling core shared with cGAS and a diversified primary ligand-binding surface modified with notable insertions and deletions. We demonstrate that surface remodelling of cGLRs enables altered ligand specificity and used a forward biochemical screen to identify cGLR1 as a double-stranded RNA sensor in the model organism Drosophila melanogaster. We show that RNA recognition activates Drosophila cGLR1 to synthesize the novel product cG[3'-5']pA[2'-5']p (3'2'-cGAMP). A crystal structure of Drosophila stimulator of interferon genes (dSTING) in complex with 3'2'-cGAMP explains selective isomer recognition, and 3'2'-cGAMP induces an enhanced antiviral state in vivo that protects from viral infection. Similar to radiation of Toll-like receptors in pathogen immunity, our results establish cGLRs as a diverse family of metazoan pattern recognition receptors.},

keywords = {imler, M3i},

pubstate = {published},

tppubtype = {article}

}

@article{Cai2021,

title = {cGAS-STING: insight on the evolution of a primordial antiviral signaling cassette},

author = {Hua Cai and Jean-Luc Imler

},

url = { https://doi.org/10.12703/r/10-54},

doi = {10.12703/r/10-54},

year  = {2021},

date = {2021-06-08},

journal = {Faculty Reviews},

volume = {10},

pages = {54},

abstract = {Stimulator of interferon genes (STING) functions in the cytosolic DNA-sensing pathway of innate immunity in mammals. It is activated upon binding the cyclic dinucleotide 2′3′-cGAMP, a second messenger produced by the enzyme cyclic guanosine monophosphate–adenosine monophosphate synthase (cGAS), which acts as the receptor for DNA in this pathway, and triggers the expression of interferons and other viral stress-induced genes. The ancient origin of STING in the evolution of animals had been noted, but its primitive function was speculative. We review here recent advances in the remarkable history of cGAS-STING signaling, which establish that cGAS is a member of the family of cGAS/DncV-like nucleotidyltransferases (CD-NTases). In bacteria, CD-NTases synthesize a wide range of cyclic oligonucleotide second messengers in response to bacteriophage infections, which in turn activate a variety of effector proteins to abort phage infection. Among these effectors, some are related to STING, revealing an ancestral function for the cGAS-STING cassette in antiviral host defense. Study of STING signaling in invertebrate animals is consistent with an early acquisition in the history of metazoans of CD-NTase- and STING-encoding genes to counter the universal threat of viruses. In particular, STING-dependent immunity appears to play a previously unsuspected important role in some insects. These discoveries open up interesting perspectives for the use of model organisms to decipher emerging aspects of cGAS-STING biology in mammals, such as the activation of interferon-independent responses or the function and regulation of cGAS in the nucleus.},

keywords = {imler, M3i},

pubstate = {published},

tppubtype = {article}

}

@article{Leite2021,

title = {Distinct Roles of Hemocytes at Different Stages of Infection by Dengue and Zika Viruses in Aedes aegypti Mosquitoes},

author = {Thiago H J F Leite and Alvaro G A Ferreira and Jean-Luc Imler and João T Marques},

url = {https://www.frontiersin.org/articles/10.3389/fimmu.2021.660873/full},

doi = {10.3389/fimmu.2021.660873},

year  = {2021},

date = {2021-05-13},

journal = {Frontiers in immunology},

volume = {12},

pages = {660873},

abstract = {Aedes aegypti mosquitoes are vectors for arboviruses of medical importance such as dengue (DENV) and Zika (ZIKV) viruses. Different innate immune pathways contribute to the control of arboviruses in the mosquito vector including RNA interference, Toll and Jak- STAT pathways. However, the role of cellular responses mediated by circulating macrophage-like cells known as hemocytes remains unclear. Here we show that hemocytes are recruited to the midgut of Ae. aegypti mosquitoes in response to DENV or ZIKV. Blockade of the phagocytic function of hemocytes using latex beads induced increased accumulation of hemocytes in the midgut and a reduction in virus infection levels in this organ. In contrast, inhibition of phagocytosis by hemocytes led to increased systemic dissemination and replication of DENV and ZIKV. Hence, our work reveals a dual role for hemocytes in Ae. aegypti mosquitoes, whereby phagocytosis is not required to control viral infection in the midgut but is essential to restrict systemic dissemination. Further understanding of the mechanism behind this duality could help the design of vector-based strategies to prevent transmission of arboviruses.},

keywords = {Aedes, Dengue, Hemocytes, imler, innate immunity, M3i, Marques, Zika},

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},

urldate = {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{H2021,

title = {Insect decline: immediate action is needed},

author = {H Jactel and JL Imler and L Lambrechts and AB Failloux and JD Lebreton and Y Le Maho and JC Duplessy and P Cossart and P Grandcolas},

url = {https://doi.org/10.5802/crbiol.37},

doi = {10.5802/crbiol.37},

issn = {17683238},

year  = {2021},

date = {2021-01-25},

journal = {Comptes Rendus. Biologies},

abstract = { Insects appeared more than 400 million years ago and they represent the richest and most diverse taxonomic group with several million species. Yet, under the combined effect of the loss of natural habitats, the intensification of agriculture with massive use of pesticides, global warming and biological invasions, insects show alarming signs of decline. Although difficult to quantify, species extinction and population reductions are confirmed for many ecosystems. This results in a loss of services such as the pollination of plants, including food crops, the recycling of organic matter, the supply of goods such as honey and the stability of food webs. It is therefore urgent to halt the decline of Insects. We recommend implementing long-term monitoring of populations, tackling the causes of insect decline by reducing the use of synthetic insecticides, preserving natural habitats, and reinventing a positive relationship between humans and insects.



Apparus il y a plus de 400 millions d’années, les Insectes représentent le groupe taxonomique le plus riche et diversifié, avec plusieurs millions d’espèces. Sous l’effet de la disparition des habitats, de l’intensification de l’agriculture avec l’usage massif des pesticides, du réchauffement climatique et des invasions biologiques, les Insectes montrent des signes alarmants de déclin. Bien que difficiles à quantifier, la disparition des espèces et la réduction de leurs populations sont avérées et communes à de nombreux écosystèmes. Elles se traduisent par une perte des services rendus, comme la pollinisa- tion des plantes vivrières, le recyclage de la matière organique, la fourniture de biens comme le miel, et l’équilibre des réseaux trophiques. Il est donc urgent de freiner le déclin des Insectes. Pour cela, il faut mettre en œuvre des suivis à long terme des populations, réduire l’usage des insecticides de syn- thèse, préserver les habitats naturels, et réinventer la relation de l’Homme à l’Insecte en revalorisant son image et ses usages.},

keywords = {imler, M3i},

pubstate = {published},

tppubtype = {article}

}

@article{Schneider2020,

title = {Sensing and signalling viral infection in drosophila},

author = {J Schneider and JL Imler},

url = {https://doi.org/10.1016/j.dci.2020.103985

},

doi = {10.1016/j.dci.2020.103985},

year  = {2020},

date = {2020-12-23},

journal = {Developmental and Comparative Immunology},

volume = {117},

abstract = {The fruitfly Drosophila melanogaster is a valuable model to unravel mechanisms of innate immunity, in particular in the context of viral infections. RNA interference, and more specifically the small interfering RNA pathway, is a major component of antiviral immunity in drosophila. In addition, the contribution of inducible transcriptional responses to the control of viruses in drosophila and other invertebrates is increasingly recognized. In particular, the recent discovery of a STING-IKKβ-Relish signalling cassette in drosophila has confirmed that NF-κB tran- scription factors play an important role in the control of viral infections, in addition to bacterial and fungal infections. Here, we review recent developments in the field, which begin to shed light on the mechanisms involved in sensing of viral infections and in signalling leading to production of antiviral effectors.},

keywords = {imler, M3i},

pubstate = {published},

tppubtype = {article}

}