期刊
CELL DEATH DISCOVERY
卷 7, 期 1, 页码 -出版社
SPRINGERNATURE
DOI: 10.1038/s41420-021-00428-w
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资金
- CNPq
- CAPES
- FAPERJ through the National Institutes of Science and Technology Program (INCT)
- Oswaldo Cruz Foundation/Fiocruz under the auspicious of Inova program
The infection by SARS-CoV-2 induces pyroptosis in human monocytes, leading to inflammation and cytokine production, which contributes to the severity of COVID-19. The study sheds light on the mechanism of monocyte death and provides insights for potential therapies to control hyper-inflammation and reduce viral replication in severe COVID-19 patients.
Infection by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been associated with leukopenia and uncontrolled inflammatory response in critically ill patients. A better comprehension of SARS-CoV-2-induced monocyte death is essential for the identification of therapies capable to control the hyper-inflammation and reduce viral replication in patients with 2019 coronavirus disease (COVID-19). Here, we show that SARS-CoV-2 engages inflammasome and triggers pyroptosis in human monocytes, experimentally infected, and from patients under intensive care. Pyroptosis associated with caspase-1 activation, IL-1 ss production, gasdermin D cleavage, and enhanced pro-inflammatory cytokine levels in human primary monocytes. At least in part, our results originally describe mechanisms by which monocytes, a central cellular component recruited from peripheral blood to respiratory tract, succumb to control severe COVID-19.
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