AUTHOR=Patel Seema , Tucker Heidi R. , Gogoi Himanshu , Mansouri Samira , Jin Lei 

TITLE=cGAS–STING and MyD88 Pathways Synergize in Ly6Chi Monocyte to Promote Streptococcus pneumoniae-Induced Late-Stage Lung IFNγ Production

JOURNAL=Frontiers in Immunology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.699702

DOI=10.3389/fimmu.2021.699702

ISSN=1664-3224

ABSTRACT=<p>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 <italic>Streptococcus pneumoniae</italic>-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 <italic>via</italic> the production of IL-12p70. Surprisingly, DNA stimulation alone could not induce IL-12p70 or IFNγ in Ly6C<sup>hi</sup> monocyte. The production of IFNγ required the activation by both DNA and heat-killed <italic>S. pneumococcus</italic>. Accordingly, MyD88<sup>−/−</sup> monocyte did not generate IL-12p70 or IFNγ. In summary, the cGAS–STING pathway synergizes with the MyD88 pathway in monocyte to promote late-stage lung IFNγ production during pulmonary pneumococcal infection.</p>