University of Massachusetts Medical School Faculty Publications

Title

Group B Streptococcus Degrades Cyclic-di-AMP to Modulate STING-Dependent Type I Interferon Production

UMMS Affiliation

Department of Medicine, Division of Infectious Diseases and Immunology; Program in Innate Immunity

Publication Date

2016-07-13

Document Type

Article

Disciplines

Bacteriology | Immunity | Pathogenic Microbiology

Abstract

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.

Keywords

Streptococcus agalactiae, c-di-AMP, cGAS, ectonucleotidase, interferon-β

DOI of Published Version

10.1016/j.chom.2016.06.003

Source

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

Related Resources

Link to Article in PubMed

Journal/Book/Conference Title

Cell host and microbe

PubMed ID

27414497

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