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

https://www.ncbi.nlm.nih.gov/pubmed/37659413

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.