Show simple item record

dc.contributor.authorAndrade, Warrison A.
dc.contributor.authorFiron, Arnaud
dc.contributor.authorSchmidt, Tobias
dc.contributor.authorHornung, Veit
dc.contributor.authorFitzgerald, Katherine A.
dc.contributor.authorKurt-Jones, Evelyn A.
dc.contributor.authorTrieu-Cuot, Patrick
dc.contributor.authorGolenbock, Douglas T.
dc.contributor.authorKaminski, Pierre-Alexandre
dc.date2022-08-11T08:08:19.000
dc.date.accessioned2022-08-23T15:51:01Z
dc.date.available2022-08-23T15:51:01Z
dc.date.issued2016-07-13
dc.date.submitted2016-09-02
dc.identifier.citationCell Host Microbe. 2016 Jul 13;20(1):49-59. doi: 10.1016/j.chom.2016.06.003. <a href="http://dx.doi.org/10.1016/j.chom.2016.06.003">Link to article on publisher's site</a>
dc.identifier.issn1931-3128 (Linking)
dc.identifier.doi10.1016/j.chom.2016.06.003
dc.identifier.pmid27414497
dc.identifier.urihttp://hdl.handle.net/20.500.14038/28797
dc.description.abstractInduction 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.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=27414497&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://dx.doi.org/10.1016/j.chom.2016.06.003
dc.subjectStreptococcus agalactiae
dc.subjectc-di-AMP
dc.subjectcGAS
dc.subjectectonucleotidase
dc.subjectinterferon-β
dc.subjectBacteriology
dc.subjectImmunity
dc.subjectPathogenic Microbiology
dc.titleGroup B Streptococcus Degrades Cyclic-di-AMP to Modulate STING-Dependent Type I Interferon Production
dc.typeJournal Article
dc.source.journaltitleCell host and microbe
dc.source.volume20
dc.source.issue1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/faculty_pubs/1036
dc.identifier.contextkey9072027
html.description.abstract<p>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.</p>
dc.identifier.submissionpathfaculty_pubs/1036
dc.contributor.departmentProgram in Innate Immunity
dc.contributor.departmentDepartment of Medicine, Division of Infectious Diseases and Immunology
dc.source.pages49-59


Files in this item

Thumbnail
Name:
Publisher version

This item appears in the following Collection(s)

Show simple item record