Journal
IMMUNITY
Volume 53, Issue 1, Pages 115-+Publisher
CELL PRESS
DOI: 10.1016/j.immuni.2020.06.009
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Funding
- National Institutes of Health [AR067135, AI134877, AI151708]
- Cancer Prevention and Research Institute of Texas (CPRIT) [RP180288]
- Burroughs Wellcome Fund
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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.
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