| First Author | Park SM | Year | 2019 |
| Journal | Commun Biol | Volume | 2 |
| Pages | 464 | PubMed ID | 31840109 |
| Mgi Jnum | J:289581 | Mgi Id | MGI:6433735 |
| Doi | 10.1038/s42003-019-0701-2 | Citation | Park SM, et al. (2019) T cell fate following Salmonella infection is determined by a STING-IRF1 signaling axis in mice. Commun Biol 2:464 |
| abstractText | The innate immune response following infection with entero-invasive bacterial species is triggered upon release of cyclic di-guanylate monophosphate (c-di-GMP) into the host cell cytosol. Bacterial c-di-GMP activates the intracellular Sensor Stimulator of Interferon Genes (STING), encoded by Tmem173 in mice. Here we identify Interferon Regulatory Factor (IRF) 1 as a critical effector of STING-mediated microbial DNA sensing that is responsible for TH17 cell generation in the mucosal immune system. We find that STING activation induces IRF1-dependent transcriptional programs in dendritic cells (DCs) that define T cell fate determination, including induction of Gasdermin D, IL-1 family member cytokines, and enzymes for eicosanoid synthesis. Our results show that IRF1-dependent transcriptional programs in DCs are a prerequisite for antigen-specific TH17 subspecification in response to microbial c-di-GMP and Salmonella typhimurium infection. Our identification of a STING-IRF1 signaling axis for adaptive host defense control will aid further understanding of infectious disease mechanisms. |
