坏死性下垂
细胞激素风暴
发病机制
炎症
免疫学
程序性细胞死亡
医学
细胞凋亡
细胞因子
弥漫性肺泡损伤
冠状病毒
免疫系统
肺
病毒
生物
病理
疾病
2019年冠状病毒病(COVID-19)
传染病(医学专业)
内科学
急性呼吸窘迫
生物化学
作者
Shufen Li,Yulan Zhang,Zhenqiong Guan,Huiling Li,Meidi Ye,Xi Chen,Jun Shen,Yiwu Zhou,Zhengli Shi,Peng Zhou,Ke Peng
标识
DOI:10.1038/s41392-020-00334-0
摘要
Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can lead to respiratory illness and multi-organ failure in critically ill patients. Although the virus-induced lung damage and inflammatory cytokine storm are believed to be directly associated with coronavirus disease 2019 (COVID-19) clinical manifestations, the underlying mechanisms of virus-triggered inflammatory responses are currently unknown. Here we report that SARS-CoV-2 infection activates caspase-8 to trigger cell apoptosis and inflammatory cytokine processing in the lung epithelial cells. The processed inflammatory cytokines are released through the virus-induced necroptosis pathway. Virus-induced apoptosis, necroptosis, and inflammation activation were also observed in the lung sections of SARS-CoV-2-infected HFH4-hACE2 transgenic mouse model, a valid model for studying SARS-CoV-2 pathogenesis. Furthermore, analysis of the postmortem lung sections of fatal COVID-19 patients revealed not only apoptosis and necroptosis but also massive inflammatory cell infiltration, necrotic cell debris, and pulmonary interstitial fibrosis, typical of immune pathogenesis in the lung. The SARS-CoV-2 infection triggered a dual mode of cell death pathways and caspase-8-dependent inflammatory responses may lead to the lung damage in the COVID-19 patients. These discoveries might assist the development of therapeutic strategies to treat COVID-19.
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