The virus-induced cyclic dinucleotide 2'3'-c-di-GMP mediates STING-dependent antiviral immunity in Drosophila.
Fiche publication
Date publication
août 2023
Journal
Immunity
Auteurs
Membres identifiés du Cancéropôle Est :
Pr IMLER Jean-Luc, Dr MEIGNIN Carine
Tous les auteurs :
Cai H, Li L, Slavik KM, Huang J, Yin T, Ai X, Hédelin L, Haas G, Xiang Z, Yang Y, Li X, Chen Y, Wei Z, Deng H, Chen D, Jiao R, Martins N, Meignin C, Kranzusch PJ, Imler JL
Lien Pubmed
Résumé
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.
Mots clés
Drosophila, STING, c-di-GMP, cGAMP, cGAS, cGLR, cyclic dinucleotide, evolution, pattern recognition receptor, virus
Référence
Immunity. 2023 08 28;: