Sting通路在炎症和Covid-19发病中的作用

B. A
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摘要

最近的Sars-Cov2 (COVID-19)遭遇表明,需要更强大的免疫系统作为身体防御机制的第一道防线。免疫反应越强,对病原体的识别就越好。更好地了解免疫反应机制及其组成部分的功能将为防御这些病原体铺平道路。先天免疫防御在本质上是非特异性的,可以识别DNA和RNA病毒以及攻击身体的其他病原体。外来核酸与特定的模式识别受体(PRRs)结合,包括toll样受体(TLRs)、cGAS-STING、nod样受体(NLR)和RNA解旋酶受体(RIG-1和MDA5),会触发信号级联反应。这些信号通路直接导致先天免疫系统产生1型干扰素和其他细胞因子/趋化因子效应物,进而激活适应性免疫反应。STING通路作为自体和非自体核酸的主要天然探测器,在炎症的发展和1型干扰素的产生中起着重要作用。COVID-19与呼吸衰竭相关,其主要特征是细胞因子风暴,导致过度炎症。这些高炎症反应加重了患者的免疫受损状态,使这种疾病成为全球死亡的主要原因。了解高炎症过程的主要机制和调控机制将为降低死亡率提供有效的治疗方法。STING通路的解除调控涉及多种炎症性疾病,这使其成为了解其在病毒攻击过程中工作机制的有效靶点。最近的许多研究进一步支持了延迟STING信号在COVID-19第二阶段发病机制中的重要性。本文主要综述了STING在炎症中的作用及其在免疫系统中的功能,这些功能可用于解决COVID-19最近的发病机制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Impact of Sting Pathway in Inflammation and Covid-19 Pathogenesis
The recent encounter by Sars-Cov2 (COVID-19) presented the need of having stronger immune system as the first line of body’s defense mechanism. Stronger the immune response better will be the pathogen recognition. Better understanding of immune response mechanism and functioning of its components will pave the route for defending against these pathogens. Innate immune defense being non-specific in nature identifies both DNA and RNA viruses as well as other pathogens attacking the body. Presence of foreign nucleic acids bound to the specific pattern recognition receptors (PRRs) which include toll-like receptors (TLRs), cGAS-STING, Nod-like receptors (NLR) and RNA helicase receptors (RIG-1 and MDA5) triggers a signaling cascade. These signaling channels direct to the production of type-1 interferons and other cytokine/chemokine effectors of innate immune system which in turn activate adaptive immune response. STING pathway as a prime innate detector of self and non-self-nucleic acids plays an important role in the development of inflammation followed by type-1 interferon production. COVID-19 being involved with the respiratory failure shows the main characteristic feature of cytokine storm which direct to hyper inflammation. These hyper-inflammatory responses worsen the immune compromised state of the patients which makes this disease as the leading cause of mortality worldwide. Understanding the underline mechanisms involved in and regulating the process of hyper inflammation would provide an effective treatment to reduce the mortalities. Deregulation of STING pathway is involved in various inflammatory diseases that make it a potent target to understand its mechanism of work during viral attack. Many recent studies have further supported the importance of delayed STING signaling in the pathogenesis of COVID-19 during the second phase of this disease. This review mainly focuses on the role of STING in inflammation and its function in our immune system which can be harnessed to tackle the recent pathogeneses of COVID-19.
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