美国圣裘德儿童研究医院Thirumala-Devi Kanneganti研究团队发现，TLR2通过感知SARS-CoV-2包膜蛋白来产生炎症细胞因子。这一研究成果于2021年5月7日在线发表在国际学术期刊《自然—免疫学》上。

研究人员发现，TLR2和MYD88的表达均与COVID-19疾病的严重程度有关。从机理上讲，β-冠状病毒诱导的炎症反应需要TLR2和Myd88，并且TLR2依赖性信号在冠状病毒感染期间不依赖于病毒进入而诱导促炎细胞因子的产生。TLR2感知到SARS-CoV-2包膜蛋白为其配体。另外，在体内阻断TLR2信号传导提供了针对SARS-CoV-2感染发病机理的保护。总体而言，这项研究对β冠状病毒感知和炎性细胞因子产生的分子机制提供了重要的了解，这为COVID-19的治疗策略研发开辟了新途径。

据了解，先天性免疫应答对于通过释放细胞因子和趋化因子来识别和控制感染至关重要。但是，某些感染（包括SARS-CoV-2）期间的严重病理是由过度活跃的细胞因子释放或细胞因子风暴驱动的。在COVID-19感染时期，对激活促炎性细胞因子和趋化因子产生的先天性传感器的表征仍然很缺乏。

附：英文原文

Title: TLR2 senses the SARS-CoV-2 envelope protein to produce inflammatory cytokines

Author: Min Zheng, Rajendra Karki, Evan Peter Williams, Dong Yang, Elizabeth Fitzpatrick, Peter Vogel, Colleen Beth Jonsson, Thirumala-Devi Kanneganti

Issue&Volume: 2021-05-07

Abstract: The innate immune response is critical for recognizing and controlling infections through the release of cytokines and chemokines. However, severe pathology during some infections, including SARS-CoV-2, is driven by hyperactive cytokine release, or a cytokine storm. The innate sensors that activate production of proinflammatory cytokines and chemokines during COVID-19 remain poorly characterized. In the present study, we show that both TLR2 and MYD88 expression were associated with COVID-19 disease severity. Mechanistically, TLR2 and Myd88 were required for β-coronavirus-induced inflammatory responses, and TLR2-dependent signaling induced the production of proinflammatory cytokines during coronavirus infection independent of viral entry. TLR2 sensed the SARS-CoV-2 envelope protein as its ligand. In addition, blocking TLR2 signaling in vivo provided protection against the pathogenesis of SARS-CoV-2 infection. Overall, our study provides a critical understanding of the molecular mechanism of β-coronavirus sensing and inflammatory cytokine production, which opens new avenues for therapeutic strategies to counteract the ongoing COVID-19 pandemic.

DOI: 10.1038/s41590-021-00937-x

Source: https://www.nature.com/articles/s41590-021-00937-x