| First Author | Wu J | Year | 2020 |
| Journal | Immunity | Volume | 53 |
| Issue | 1 | Pages | 115-126.e5 |
| PubMed ID | 32640258 | Mgi Jnum | J:304742 |
| Mgi Id | MGI:6693948 | Doi | 10.1016/j.immuni.2020.06.009 |
| Citation | Wu J, et al. (2020) Interferon-Independent Activities of Mammalian STING Mediate Antiviral Response and Tumor Immune Evasion. Immunity 53(1):115-126.e5 |
| abstractText | Type I interferon (IFN) response is commonly recognized as the main signaling activity of STING. Here, we generate the Sting1(S365A/S365A) mutant mouse that precisely ablates IFN-dependent activities while preserving IFN-independent activities of STING. Sting(S365A/S365A) mice protect against HSV-1 infection, despite lacking the STING-mediated IFN response. This challenges the prevailing view and suggests that STING controls HSV-1 infection through IFN-independent activities. Transcriptomic analysis reveals widespread IFN-independent activities of STING in macrophages and T cells, and STING activities in T cells are predominantly IFN independent. In mouse tumor models, T cells in the tumor experience substantial cell death that is in part mediated by IFN-independent activities of STING. We found that the tumor induces STING-mediated cell death in T cells to evade immune control. Our data demonstrate that mammalian STING possesses widespread IFN-independent activities that are important for restricting HSV-1 infection, tumor immune evasion and likely also adaptive immunity. |
