SARS-CoV-2 engages inflammasome and pyroptosis in human primary monocytes
André C. Ferreira, Vinícius Cardoso Soares, Isaclaudia G. Azevedo-Quintanilha, Suelen da Silva Gomes Dias, Natalia Fintelman‐Rodrigues, Carolina Q. Sacramento, Mayara Mattos, Caroline S. de Freitas, Jairo R. Temerozo, Lívia Teixeira, Eugênio D. Hottz, Ester A. Barreto, Camila R. R. Pão, Lohanna Palhinha, Milene Dias Miranda, Dumith Chequer Bou‐Habib, Fernando A. Bozza, Patrı́cia T. Bozza, Thiago Moreno L. Souza
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.