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Molecular and spatial mechanisms governing STING signalling
The FEBS Journal ( IF 5.5 ) Pub Date : 2020-11-25 , DOI: 10.1111/febs.15640
Katherine R Balka 1 , Dominic De Nardo 1
Affiliation  

Detection of microbial nucleic acids via innate immune receptors is critical for establishing host defence against pathogens. The DNA-sensing cGAS-STING pathway has gained increasing attention in the last decade as a key pathway for combating viral and bacterial infections. cGAS-STING activation primarily promotes the secretion of antiviral type I IFNs via the key transcription factor, IRF3. In addition, cGAS-STING signalling also elicits proinflammatory cytokines through NF-κB activity. Activation of IRF3 and NF-κB is mediated by the chief signalling receptor protein STING. Interestingly, STING undergoes significant trafficking events across multiple subcellular locations, which regulates both the activation of downstream signalling pathways, as well as appropriate termination of the responses. Studies to date have provided a comprehensive view of the regulation and role of the IRF3-IFN pathway downstream of STING. However, many aspects of STING signalling remain relatively poorly defined. This review will explore the current understanding of the mechanisms through which STING elicits inflammatory and antimicrobial responses, focusing on the precise signalling and intracellular trafficking events that occur. We will also discuss exciting and emerging concepts in the field, including the importance of IFN-independent STING responses for host defence and during STING-related disease.

中文翻译:

控制 STING 信号的分子和空间机制

通过先天免疫受体检测微生物核酸对于建立针对病原体的宿主防御至关重要。在过去十年中,DNA 感应 cGAS-STING 通路作为对抗病毒和细菌感染的关键通路受到越来越多的关注。cGAS-STING 激活主要通过关键转录因子 IRF3 促进抗病毒 I 型干扰素的分泌。此外,cGAS-STING 信号还通过 NF-κB 活性引发促炎细胞因子。IRF3 和 NF-κB 的激活由主要信号受体蛋白 STING 介导。有趣的是,STING 经历了跨多个亚细胞位置的重大运输事件,这调节了下游信号通路的激活以及响应的适当终止。迄今为止的研究对 STING 下游 IRF3-IFN 通路的调节和作用提供了全面的观点。然而,STING 信号的许多方面仍然相对不明确。本综述将探讨目前对 STING 引发炎症和抗菌反应机制的理解,重点关注发生的精确信号传导和细胞内运输事件。我们还将讨论该领域令人兴奋的新兴概念,包括不依赖 IFN 的 STING 反应对宿主防御和 STING 相关疾病期间的重要性。本综述将探讨目前对 STING 引发炎症和抗菌反应机制的理解,重点关注发生的精确信号传导和细胞内运输事件。我们还将讨论该领域令人兴奋的新兴概念,包括不依赖 IFN 的 STING 反应对宿主防御和 STING 相关疾病期间的重要性。本综述将探讨目前对 STING 引发炎症和抗菌反应机制的理解,重点关注发生的精确信号传导和细胞内运输事件。我们还将讨论该领域令人兴奋的新兴概念,包括不依赖 IFN 的 STING 反应对宿主防御和 STING 相关疾病期间的重要性。
更新日期:2020-11-25
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