| First Author | Patel S | Year | 2021 |
| Journal | Front Immunol | Volume | 12 |
| Pages | 699702 | PubMed ID | 34512626 |
| Mgi Jnum | J:314253 | Mgi Id | MGI:6765878 |
| Doi | 10.3389/fimmu.2021.699702 | Citation | Patel S, et al. (2021) cGAS-STING and MyD88 Pathways Synergize in Ly6C(hi) Monocyte to Promote Streptococcus pneumoniae-Induced Late-Stage Lung IFNgamma Production. Front Immunol 12:699702 |
| abstractText | 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 IFNgamma production. Using knockout mice, IFNgamma reporter mice, intracellular cytokine staining, and adoptive cell transfer, we showed that cGAS-STING-dependent lung IFNgamma production was independent of type I IFNs. Furthermore, STING expression in monocyte/monocyte-derived cells governed IFNgamma production in the lung via the production of IL-12p70. Surprisingly, DNA stimulation alone could not induce IL-12p70 or IFNgamma in Ly6C(hi) monocyte. The production of IFNgamma required the activation by both DNA and heat-killed S. pneumococcus. Accordingly, MyD88(-/-) monocyte did not generate IL-12p70 or IFNgamma. In summary, the cGAS-STING pathway synergizes with the MyD88 pathway in monocyte to promote late-stage lung IFNgamma production during pulmonary pneumococcal infection. |
