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环鸟苷酸-干扰素基因刺激物(cGAS/STING)信号通路的调控及其相关免疫逃逸策略。

Regulation of cGAS/STING signaling and corresponding immune escape strategies of viruses.

机构信息

School of Sport, Shenzhen University, Shenzhen, China.

Key Laboratory of Adolescent Health Assessment and Exercise Intervention of Ministry of Education, East China Normal University, Shanghai, China.

出版信息

Front Cell Infect Microbiol. 2022 Sep 14;12:954581. doi: 10.3389/fcimb.2022.954581. eCollection 2022.

Abstract

Innate immunity is the first line of defense against invading external pathogens, and pattern recognition receptors (PRRs) are the key receptors that mediate the innate immune response. Nowadays, there are various PRRs in cells that can activate the innate immune response by recognizing pathogen-related molecular patterns (PAMPs). The DNA sensor cGAS, which belongs to the PRRs, plays a crucial role in innate immunity. cGAS detects both foreign and host DNA and generates a second-messenger cGAMP to mediate stimulator of interferon gene (STING)-dependent antiviral responses, thereby exerting an antiviral immune response. However, the process of cGAS/STING signaling is regulated by a wide range of factors. Multiple studies have shown that viruses directly target signal transduction proteins in the cGAS/STING signaling through viral surface proteins to impede innate immunity. It is noteworthy that the virus utilizes these cGAS/STING signaling regulators to evade immune surveillance. Thus, this paper mainly summarized the regulatory mechanism of the cGAS/STING signaling pathway and the immune escape mechanism of the corresponding virus, intending to provide targeted immunotherapy ideas for dealing with specific viral infections in the future.

摘要

先天免疫是抵御入侵外源病原体的第一道防线,模式识别受体 (PRRs) 是介导先天免疫反应的关键受体。如今,细胞中有多种 PRRs,它们可以通过识别病原体相关分子模式 (PAMPs) 来激活先天免疫反应。属于 PRRs 的 DNA 传感器 cGAS 在先天免疫中起着至关重要的作用。cGAS 可以检测外来和宿主 DNA,并生成第二信使 cGAMP 来介导干扰素基因刺激物 (STING) 依赖性抗病毒反应,从而发挥抗病毒免疫反应。然而,cGAS/STING 信号通路的过程受到广泛的因素调节。多项研究表明,病毒通过病毒表面蛋白直接靶向 cGAS/STING 信号通路中的信号转导蛋白,从而阻碍先天免疫。值得注意的是,病毒利用这些 cGAS/STING 信号通路调节剂来逃避免疫监视。因此,本文主要总结了 cGAS/STING 信号通路的调节机制和相应病毒的免疫逃逸机制,旨在为未来针对特定病毒感染提供靶向免疫治疗的思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/381a/9516114/35efb0684eb8/fcimb-12-954581-g001.jpg

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