先天免疫反应、微环境蛋白酶与COVID-19大流行:病理生理机制和新出现的治疗靶点

IF 19.3 2区 医学 Q1 UROLOGY & NEPHROLOGY Kidney International Supplements Pub Date : 2022-04-01 DOI:10.1016/j.kisu.2021.12.001
Morley D. Hollenberg , Murray Epstein
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引用次数: 10

摘要

2019冠状病毒病(COVID-19)大流行在全球范围内造成了相当大的死亡率和发病率,生物医学界已充分参与试图阐明COVID-19的病理生理学并制定强有力的治疗策略。为此,主要的研究重点是mRNA和蛋白疫苗对COVID-19感染的适应性免疫反应以及免疫保护的持续时间和持久性。相比之下,先天免疫反应对病毒攻击的作用一直被低估。本综述侧重于对COVID-19感染的先天免疫反应,重点关注细胞外蛋白酶在组织微环境中的作用。由细胞外微环境中的酶引起的蛋白酶介导的信号传导发生在介导COVID-19病理的炎症细胞因子产生增加的上游。这些酶包括凝血级联、产生激肽的血浆钾化管和补体系统,以及肾素-血管紧张素系统中产生血管紧张素的蛋白酶。此外,在本增刊中有几篇文章阐明和详细介绍了各种纤维化途径的发展轨迹,我们推断了这些见解,以探索纤维化和纤维化途径如何在COVID-19的发病机制中发挥重要作用。我们建议,从了解微环境蛋白酶在触发COVID-19病理先天免疫反应中的作用中获得的经验教训将确定潜在的治疗靶点,并为COVID-19的临床管理提供方法。此外,这些信息还可以为理解急性感染(所谓的“长COVID”)解决后可能出现的COVID-19诱导组织纤维化的决定因素提供模板,这对我们的医疗保健系统构成了重大的新挑战。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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The innate immune response, microenvironment proteinases, and the COVID-19 pandemic: pathophysiologic mechanisms and emerging therapeutic targets

The coronavirus disease 2019 (COVID-19) pandemic, causing considerable mortality and morbidity worldwide, has fully engaged the biomedical community in attempts to elucidate the pathophysiology of COVID-19 and develop robust therapeutic strategies. To this end, the predominant research focus has been on the adaptive immune response to COVID-19 infections stimulated by mRNA and protein vaccines and on the duration and persistence of immune protection. In contrast, the role of the innate immune response to the viral challenge has been underrepresented. This overview focuses on the innate immune response to COVID-19 infection, with an emphasis on the roles of extracellular proteases in the tissue microenvironment. Proteinase-mediated signaling caused by enzymes in the extracellular microenvironment occurs upstream of the increased production of inflammatory cytokines that mediate COVID-19 pathology. These enzymes include the coagulation cascade, kinin-generating plasma kallikrein, and the complement system, as well as angiotensin-generating proteinases of the renin–angiotensin system. Furthermore, in the context of several articles in this Supplement elucidating and detailing the trajectory of diverse profibrotic pathways, we extrapolate these insights to explore how fibrosis and profibrotic pathways participate importantly in the pathogenesis of COVID-19. We propose that the lessons garnered from understanding the roles of microenvironment proteinases in triggering the innate immune response to COVID-19 pathology will identify potential therapeutic targets and inform approaches to the clinical management of COVID-19. Furthermore, the information may also provide a template for understanding the determinants of COVID-19–induced tissue fibrosis that may follow resolution of acute infection (so-called “long COVID”), which represents a major new challenge to our healthcare systems.

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来源期刊
Kidney International Supplements
Kidney International Supplements UROLOGY & NEPHROLOGY-
CiteScore
11.80
自引率
0.00%
发文量
13
期刊介绍: Kidney International Supplements is published on behalf of the International Society of Nephrology (ISN) and comes complimentary as part of a subscription to Kidney International. Kidney International Supplements is a peer-reviewed journal whose focus is sponsored, topical content of interest to the nephrology community.
期刊最新文献
Editorial Board Table of Contents Variations in kidney care management and access: regional assessments of the 2023 International Society of Nephrology Global Kidney Health Atlas (ISN-GKHA) Update on variability in organization and structures of kidney care across world regions Capacity for the management of kidney failure in the International Society of Nephrology Newly Independent States and Russia region: report from the 2023 ISN Global Kidney Health Atlas (ISN-GKHA)
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