tetano
Editor, Senior Moderator
Signal Transduct Target Ther
. 2020 Oct 9;5(1):235.
doi: 10.1038/s41392-020-00334-0.
SARS-CoV-2 triggers inflammatory responses and cell death through caspase-8 activation
Shufen Li[SUP] 1 [/SUP], Yulan Zhang[SUP] 1 [/SUP], Zhenqiong Guan[SUP] 1 2 [/SUP], Huiling Li[SUP] 1 2 [/SUP], Meidi Ye[SUP] 1 2 [/SUP], Xi Chen[SUP] 3 [/SUP], Jun Shen[SUP] 4 [/SUP], Yiwu Zhou[SUP] 5 [/SUP], Zheng-Li Shi[SUP] 1 2 [/SUP], Peng Zhou[SUP] 6 7 [/SUP], Ke Peng[SUP] 8 9 [/SUP]
Affiliations
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.
. 2020 Oct 9;5(1):235.
doi: 10.1038/s41392-020-00334-0.
SARS-CoV-2 triggers inflammatory responses and cell death through caspase-8 activation
Shufen Li[SUP] 1 [/SUP], Yulan Zhang[SUP] 1 [/SUP], Zhenqiong Guan[SUP] 1 2 [/SUP], Huiling Li[SUP] 1 2 [/SUP], Meidi Ye[SUP] 1 2 [/SUP], Xi Chen[SUP] 3 [/SUP], Jun Shen[SUP] 4 [/SUP], Yiwu Zhou[SUP] 5 [/SUP], Zheng-Li Shi[SUP] 1 2 [/SUP], Peng Zhou[SUP] 6 7 [/SUP], Ke Peng[SUP] 8 9 [/SUP]
Affiliations
- PMID: 33037188
- DOI: 10.1038/s41392-020-00334-0
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.