Streptococcal M protein promotes IL-10 production by cGAS-independent activation of the STING signaling pathway

Elin Movert, Julia Lienard, Christine Valfridsson, Therése Nordström, Bengt Johansson-Lindbom, Fredric Carlsson

Research output: Contribution to journalArticlepeer-review

12 Citations (SciVal)

Abstract

From an evolutionary point of view a pathogen might benefit from regulating the inflammatory response, both in order to facilitate establishment of colonization and to avoid life-threatening host manifestations, such as septic shock. In agreement with this notion Streptococcus pyogenes exploits type I IFN-signaling to limit detrimental inflammation in infected mice, but the host-pathogen interactions and mechanisms responsible for induction of the type I IFN response have remained unknown. Here we used a macrophage infection model and report that S. pyogenes induces anti-inflammatory IL-10 in an M protein-dependent manner, a function that was mapped to the B- and C-repeat regions of the M5 protein. Intriguingly, IL-10 was produced downstream of type I IFN-signaling, and production of type I IFN occurred via M protein-dependent activation of the STING signaling pathway. Activation of STING was independent of the cytosolic double stranded DNA sensor cGAS, and infection did not induce detectable release into the cytosol of either mitochondrial, nuclear or bacterial DNA–indicating DNA-independent activation of the STING pathway in S. pyogenes infected macrophages. These findings provide mechanistic insight concerning how S. pyogenes induces the type I IFN response and identify a previously unrecognized macrophage-modulating role for the streptococcal M protein that may contribute to curb the inflammatory response to infection.

Original languageEnglish
Article numbere1006969
JournalPLoS Pathogens
Volume14
Issue number3
DOIs
Publication statusPublished - 2018 Mar 1

Subject classification (UKÄ)

  • Microbiology in the medical area
  • Immunology

Fingerprint

Dive into the research topics of 'Streptococcal M protein promotes IL-10 production by cGAS-independent activation of the STING signaling pathway'. Together they form a unique fingerprint.

Cite this