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Published on: May 21, 2018
SARS-CoV-2 engages inflammasome and pyroptosis in human primary monocytes
André C Ferreira1,2,3, Vinicius Cardoso Soares4,5, Isaclaudia G de Azevedo-Quintanilha4
1Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz (IOC), Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro, RJ, Brazil. tmoreno@cdts.fiocruz.br.
Abstract:
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-1ß 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.
Insights
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection triggers pyroptosis, a form of programmed cell death, in human monocytes. Understanding this process is key to developing therapies for severe COVID-19.
Area of Science:
- Immunology
- Virology
- Cellular Biology
Background:
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is linked to leukopenia and hyper-inflammation in critically ill patients.
- Understanding monocyte death mechanisms is crucial for developing effective COVID-19 therapies.
Purpose of the Study:
- To investigate the role of inflammasome activation and pyroptosis in SARS-CoV-2-infected human monocytes.
- To elucidate the cellular mechanisms underlying severe COVID-19 pathogenesis.
Main Methods:
- Experimental infection of human primary monocytes with SARS-CoV-2.
- Analysis of inflammasome components, including caspase-1 activation.
- Measurement of IL-1ß production and gasdermin D cleavage.
- Assessment of pro-inflammatory cytokine levels.
Main Results:
- SARS-CoV-2 infection engages the inflammasome in human monocytes.
- The virus triggers pyroptosis, characterized by caspase-1 activation and IL-1ß release.
- Gasdermin D cleavage and elevated pro-inflammatory cytokines were observed.
- These events occurred in both experimentally infected monocytes and those from intensive care COVID-19 patients.
Conclusions:
- SARS-CoV-2 induces pyroptosis in human monocytes via inflammasome activation.
- This monocyte death pathway contributes to hyper-inflammation in severe COVID-19.
- Targeting pyroptosis may offer a therapeutic strategy to control severe COVID-19.
