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M3i
Modèles Insectes d’Immunité Innée
Publications
2023
H Cai, L Li, KM Slavik, J Huang, T Yin, X Ai, L Hédelin, G Haas, Z Xiang, Y Yang, X Li, Y Chen, Z Wei, H Deng, D Chen, R Jiao, N Martins, C Meignin, PJ Kranzusch, JL Imler
The virus-induced cyclic dinucleotide 2'3'-c-di-GMP mediates STING-dependent antiviral immunity in Drosophila Article de journal
Dans: Immunity, vol. 56, iss. 9, p. 1991-2005, 2023.
Résumé | Liens | BibTeX | Étiquettes: c-di-GMP, cGAMP, cGAS, cGLR, cyclic dinucleotide, Drosophila, Evolution, Hua, imler, M3i, meignin, pattern recognition receptor, STING, virus
@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}
}
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.
2020
Cai H, Holleufer A, Simonsen B, Schneider J, Lemoine A, Gad HH, Huang J, Huang J, Chen D, Peng T, Marques JT, Hartmann R, Martins N, Imler JL
2'3'-cGAMP triggers a STING- and NF-κB-dependent broad antiviral response in Drosophila Article de journal
Dans: Science Signaling, vol. 13, no. 660, p. eabc4537, 2020.
Résumé | Liens | BibTeX | Étiquettes: imler, M3i, Marques, STING
@article{Cai_2020,
title = {2'3'-cGAMP triggers a STING- and NF-κB-dependent broad antiviral response in Drosophila},
author = {H Cai and A Holleufer and B Simonsen and J Schneider and A Lemoine and HH Gad and J Huang and J Huang and D Chen and T Peng and JT Marques and R Hartmann and N Martins and JL Imler},
url = {https://pubmed.ncbi.nlm.nih.gov/33262294/},
doi = {10.1126/scisignal.abc4537 },
year = {2020},
date = {2020-12-01},
journal = {Science Signaling},
volume = {13},
number = {660},
pages = {eabc4537},
abstract = {We previously reported that an ortholog of STING regulates infection by picorna-like viruses in Drosophila In mammals, STING is activated by the cyclic dinucleotide 2'3'-cGAMP produced by cGAS, which acts as a receptor for cytosolic DNA. Here, we showed that injection of flies with 2'3'-cGAMP induced the expression of dSTING-regulated genes. Coinjection of 2'3'-cGAMP with a panel of RNA or DNA viruses resulted in substantially reduced viral replication. This 2'3'-cGAMP-mediated protection was still observed in flies with mutations in Atg7 and AGO2, genes that encode key components of the autophagy and small interfering RNA pathways, respectively. By contrast, this protection was abrogated in flies with mutations in the gene encoding the NF-κB transcription factor Relish. Transcriptomic analysis of 2'3'-cGAMP-injected flies revealed a complex response pattern in which genes were rapidly induced, induced after a delay, or induced in a sustained manner. Our results reveal that dSTING regulates an NF-κB-dependent antiviral program that predates the emergence of interferons in vertebrates. },
keywords = {imler, M3i, Marques, STING},
pubstate = {published},
tppubtype = {article}
}
We previously reported that an ortholog of STING regulates infection by picorna-like viruses in Drosophila In mammals, STING is activated by the cyclic dinucleotide 2'3'-cGAMP produced by cGAS, which acts as a receptor for cytosolic DNA. Here, we showed that injection of flies with 2'3'-cGAMP induced the expression of dSTING-regulated genes. Coinjection of 2'3'-cGAMP with a panel of RNA or DNA viruses resulted in substantially reduced viral replication. This 2'3'-cGAMP-mediated protection was still observed in flies with mutations in Atg7 and AGO2, genes that encode key components of the autophagy and small interfering RNA pathways, respectively. By contrast, this protection was abrogated in flies with mutations in the gene encoding the NF-κB transcription factor Relish. Transcriptomic analysis of 2'3'-cGAMP-injected flies revealed a complex response pattern in which genes were rapidly induced, induced after a delay, or induced in a sustained manner. Our results reveal that dSTING regulates an NF-κB-dependent antiviral program that predates the emergence of interferons in vertebrates.
Goto Akira, Okado Kiyoshi, Martins Nelson, Cai Hua, Barbier Vincent, Lamiable Olivier, Troxler Laurent, Santiago Estelle, Kuhn Lauriane, Paik Donggi, Silverman Neal, Holleufer Andreas, Hartmann Rune, Liu Jiyong, Peng Tao, Hoffmann Jules A, Meignin Carine, Daeffler Laurent, Imler Jean-Luc
The Kinase IKKβ Regulates a STING-and NF-κB-Dependent Antiviral Response Pathway in Drosophila Article de journal
Dans: Immunity, vol. 52, no. 1, p. 200, 2020.
Résumé | Liens | BibTeX | Étiquettes: antiviral, Drosophila, hoffmann, imler, Kinase, M3i, meignin, STING
@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}
}
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.