Fiche publication
Date publication
juillet 2021
Journal
Nature
Auteurs
Membres identifiés du Cancéropôle Est :
Pr IMLER Jean-Luc
Tous les auteurs :
Holleufer A, Winther KG, Gad HH, Ai X, Chen Y, Li L, Wei Z, Deng H, Liu J, Frederiksen NA, Simonsen B, Andersen LL, Kleigrewe K, Dalskov L, Pichlmair A, Cai H, Imler JL, Hartmann R
Lien Pubmed
Résumé
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 prokaryotes and eukaryotes. In bacteria, these enzymes synthesize a range of cyclic oligonucleotide and have recently emerged as important regulators of phage infections. 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.
Référence
Nature. 2021 Jul 14;:
