CGAS-STING and MyD88 Pathways Synergize in Ly6C^hi Monocyte to Promote Streptococcus pneumoniae-Induced Late-Stage Lung IFNγ Production.

ABSTRACT: The cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway senses DNA and induces type I interferon (IFN) production. Whether and how the STING pathway crosstalk to other innate immune pathways during pathogen infection, however, remains unclear. Here, we showed that STING was needed for Streptococcus pneumoniae-induced late, not early, stage of lung IFNγ production. Using knockout mice, IFNγ reporter mice, intracellular cytokine staining, and adoptive cell transfer, we showed that cGAS-STING-dependent lung IFNγ production was independent of type I IFNs. Furthermore, STING expression in monocyte/monocyte-derived cells governed IFNγ production in the lung via the production of IL-12p70. Surprisingly, DNA stimulation alone could not induce IL-12p70 or IFNγ

SUBMITTER: Patel S 

PROVIDER: S-EPMC8427188 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature