哺乳动物 STING 的干扰素非依赖性活性介导抗病毒反应和肿瘤免疫逃逸。
Interferon-Independent Activities of Mammalian STING Mediate Antiviral Response and Tumor Immune Evasion.
机构信息
Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
出版信息
Immunity. 2020 Jul 14;53(1):115-126.e5. doi: 10.1016/j.immuni.2020.06.009. Epub 2020 Jul 7.
Type I interferon (IFN) response is commonly recognized as the main signaling activity of STING. Here, we generate the Sting1 mutant mouse that precisely ablates IFN-dependent activities while preserving IFN-independent activities of STING. Sting 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.
I 型干扰素 (IFN) 反应通常被认为是 STING 的主要信号活动。在这里，我们生成了 Sting1 突变小鼠，该小鼠可精确消除 IFN 依赖性活性，同时保留 STING 的 IFN 非依赖性活性。Sting 小鼠可预防 HSV-1 感染，尽管缺乏 STING 介导的 IFN 反应。这对流行观点提出了挑战，并表明 STING 通过 IFN 非依赖性活性控制 HSV-1 感染。转录组分析揭示了 STING 在巨噬细胞和 T 细胞中广泛的 IFN 非依赖性活性，并且 T 细胞中的 STING 活性主要是非 IFN 依赖性的。在小鼠肿瘤模型中，肿瘤中的 T 细胞经历了大量的细胞死亡，其中部分是由 STING 的 IFN 非依赖性活性介导的。我们发现肿瘤诱导 T 细胞中的 STING 介导的细胞死亡以逃避免疫控制。我们的数据表明，哺乳动物 STING 具有广泛的 IFN 非依赖性活性，对于限制 HSV-1 感染、肿瘤免疫逃逸以及可能还有适应性免疫至关重要。
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