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

Andrade WA, Firon A, Schmidt T, Hornung V, Fitzgerald KA, Kurt-Jones EA, Trieu-Cuot P, Golenbock DT, Kaminski PA.

Cell Host & Microbe 20, 49–59, 2016

Speaker: Hsin-Hua Lu (盧信樺)                                   Time: 15:00~16:00, May. 10, 2017

Commentator: Dr. Jenn-Wei Chen (陳振暐老師)        Place: Room 601

Abstract

Type I interferons (IFNs), the well-known antiviral cytokines in host defense, also play an important role in response to bacterial infection.¹ Infection of intracellular pathogens, such as viruses and intracellular bacteria, can trigger type I IFNs production by cGAS/STING pathway.² The presence of DNA in cytoplasm activates cGAS, while STING is activated by cyclic dinucleotides (cdNs) produced by cGAS or derived from bacterial origins. Previous studies showed that cdNs served as second messengers regulating both intra- and extracellular signalings in many bacteria. In this study, the authors demonstrated that Group B Streptococcus (GBS), the extracellular pathogens, can also activate cGAS/STING pathway to produce type I IFNs by releasing cyclic-di-AMP via non-specific transporters. To counteract this host defense pathway, GBS produces theectonucleotidase CdnP on cell surface to hydrolyze bacterial cyclic-di-AMP and reduce type I IFNs production. In contrast, inactivation of CdnP leads to c-di-AMP accumulation outside GBS, resulting in a high level of IFN-b in vitro and in vivo. Moreover, the authors found that GBS-induced IFN-b is STING-dependent but cGAS-independent. In conclusion, bacteria-derived cdNs can be directly sensed by STING. GBS utilizes CdnP to overcome this STING-dependent IFN induction by digesting c-di-AMP derived from itself.

References:

(1)  Archer, K.A., Durack, J., and Portnoy, D.A. (2014). STING-dependent type I IFN production inhibits cell-mediated immunity to Listeria monocytogenes.PLoS Pathog. 10, e1003861

(2)  Barber, G.N. (2014). STING-dependent cytosolic DNA sensing pathways. Trends Immunol. 35, 88–93.