UMass Chan 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
Journal/Book/Conference Title
Cell host and microbe
PubMed ID
27414497
Repository Citation
Andrade WA, Firon A, Schmidt T, Hornung V, Fitzgerald KA, Kurt-Jones EA, Trieu-Cuot P, Golenbock DT, Kaminski P. (2016). Group B Streptococcus Degrades Cyclic-di-AMP to Modulate STING-Dependent Type I Interferon Production. UMass Chan Medical School Faculty Publications. https://doi.org/10.1016/j.chom.2016.06.003. Retrieved from https://escholarship.umassmed.edu/faculty_pubs/1036