Group B Streptococcus Degrades Cyclic-di-AMP to Modulate STING-Dependent Type I Interferon Production
Department of Medicine, Division of Infectious Diseases and Immunology; Program in Innate Immunity
Bacteriology | Immunity | Pathogenic Microbiology
Induction of type I interferon (IFN) in response to microbial pathogens depends on a conserved cGAS-STING signaling pathway. The presence of DNA in the cytoplasm activates cGAS, while STING is activated by cyclic dinucleotides (cdNs) produced by cGAS or from bacterial origins. Here, we show that Group B Streptococcus (GBS) induces IFN-beta production almost exclusively through cGAS-STING-dependent recognition of bacterial DNA. However, we find that GBS expresses an ectonucleotidase, CdnP, which hydrolyzes extracellular bacterial cyclic-di-AMP. Inactivation of CdnP leads to c-di-AMP accumulation outside the bacteria and increased IFN-beta production. Higher IFN-beta levels in vivo increase GBS killing by the host. The IFN-beta overproduction observed in the absence of CdnP is due to the cumulative effect of DNA sensing by cGAS and STING-dependent sensing of c-di-AMP. These findings describe the importance of a bacterial c-di-AMP ectonucleotidase and suggest a direct bacterial mechanism that dampens activation of the cGAS-STING axis.
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Citation: Cell Host Microbe. 2016 Jul 13;20(1):49-59. doi: 10.1016/j.chom.2016.06.003. Link to article on publisher's site
Streptococcus agalactiae, c-di-AMP, cGAS, ectonucleotidase, interferon-β
Cell host and microbe
Andrade, Warrison A.; Firon, Arnaud; Schmidt, Tobias; Hornung, Veit; Fitzgerald, Katherine A.; Kurt-Jones, Evelyn A.; Trieu-Cuot, Patrick; Golenbock, Douglas T.; and Kaminski, Pierre-Alexandre, "Group B Streptococcus Degrades Cyclic-di-AMP to Modulate STING-Dependent Type I Interferon Production" (2016). University of Massachusetts Medical School Faculty Publications. 1036.