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.
Highlights
Severe acute respiratory coronavirus 2 (SARS-CoV-2), the etiological agent of the 2019 coronavirus disease (COVID-19), emerged in China, causing a major public health burden in decades
To other respiratory viruses[29,30,31], SARS-CoV-2 induces a cytokine storm, characterized by an uncontrolled inflammatory response mediated by monocytes/macrophages, when they should orchestrate the antiviral immune response[32]
We demonstrate that SARS-CoV-2 engages inflammasome, with subsequent caspase-1 activation, increase IL-1ß levels and gasdermin D (GSDMD) pore formation in human primary monocytes, pointing toward a pyroptotic cell death
Summary
Severe acute respiratory coronavirus 2 (SARS-CoV-2), the etiological agent of the 2019 coronavirus disease (COVID-19), emerged in China, causing a major public health burden in decades. Patients with severe COVID-19 may present an asymptomatic/mild disease, others experience acute respiratory distress syndrome (ARDS) characterized by elevated serum levels of proinflammatory mediators—the cytokine storm[1,2,3]. High LDH levels and leukopenia in severe COVID-19 points out that white cells loses the integrity of plasma membrane[8,9,10,11]. Among these cells, monocytes should orchestrate the equilibrium between innate and adaptative immune responses, which may be presumably affected during cytokine storm.
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