Interferon-Independent Activities of Mammalian STING Mediate Antiviral Response and Tumor Immune Evasion
Open accessAbstract
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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On reaching the Golgi, STING recruits TBK1, which activates IRF3 and NF-κB, leading to expression of ISGs, type I interferons and other inflammatory cytokines.
“On reaching the Golgi compartment, STING then recruits TBK1, which then activates IRF3 and NF-κB, leading to the expression of interferon-stimulated genes (ISGs), type I interferons and other inflammatory cytokines (e.g., IL-6, IL-12).393–396”
From Role of neuroinflammation in neurodegeneration development (2023) · cites this paper as [396]
The Introduction (page unavailable) says STING moves to the ER-Golgi intermediate compartment and Golgi, recruits TBK1, and activates the TBK1–IRF3–type I interferon pathway. The Results (page unavailable) report STING-dependent ISG expression, NF-κB signaling, and inflammatory cytokines including IL-6. They do not establish that TBK1 activates NF-κB or identify IL-12 as an induced cytokine. (LLM, conf=0.85)
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- Authors
- Wu, J., Dobbs, N., Yang, K., & Yan, N.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- Corresponding author
- Yan, Nan
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2020-07
- Volume
- 53
- Issue
- 1
- Pages
- 115-126.e5
- ISSN
- 1074-7613 (ISSN-L)
- PMC
- PMC7365768
- OpenAlex
- W3038995504
- Cited by
- 373
- References
- 37
- Citations by year
- 2026: 53 · 2025: 69 · 2024: 84 · 2023: 64 · 2022: 62 · 2021: 33 · 2020: 8
- FWCI
- 14.89
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Burroughs Wellcome Fund
- National Institutes of Health
- Cancer Prevention and Research Institute of Texas
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- STING, type I interferon response, HSV-1 infection, antiviral immunity, tumor immune evasion, T cell death, macrophages, innate immunity, adaptive immunity
- MeSH terms
- STING Protein, Animals, Cell Line, Female, Herpes Simplex, Humans, Immunity, Innate, Interferon Type I, Macrophages, Male, Membrane Proteins, Mice, Inbred C57BL, Neoplasms, T-Lymphocytes, Signal Transduction, Herpesvirus 1, Human, Mice, Knockout, Tumor Escape, Mice, Adaptive Immunity, HEK293 Cells
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