Human NLRP1 is a sensor of pathogenic coronavirus 3CL proteases in lung epithelial cells

Rémi Planès, Miriam Pinilla, Karin Santoni, Audrey Hessel, Charlotte Passemar, Kenneth Lay, Perrine Paillette, Ana Luiza Chaves Valadão, Kim Samirah Robinson, Paul Bastard, Nathaniel Lam, Ricardo Fadrique, Ida Rossi, David Pericat, Salimata Bagayoko, Stephen Adonai Leon-Icaza, Yoann Rombouts, Eric Perouzel, Michèle Tiraby, Qian ZhangPietro Cicuta, Emmanuelle Jouanguy, Olivier Neyrolles, Clare E. Bryant, Andres R. Floto, Caroline Goujon, Franklin Zhong Lei, Guillaume Martin-Blondel, Stein Silva, Jean Laurent Casanova, Céline Cougoule, Bruno Reversade, Julien Marcoux, Emmanuel Ravet, Etienne Meunier

Research output: Contribution to journalArticlepeer-review

44 Scopus citations


Inflammation observed in SARS-CoV-2-infected patients suggests that inflammasomes, proinflammatory intracellular complexes, regulate various steps of infection. Lung epithelial cells express inflammasome-forming sensors and constitute the primary entry door of SARS-CoV-2. Here, we describe that the NLRP1 inflammasome detects SARS-CoV-2 infection in human lung epithelial cells. Specifically, human NLRP1 is cleaved at the Q333 site by multiple coronavirus 3CL proteases, which triggers inflammasome assembly and cell death and limits the production of infectious viral particles. Analysis of NLRP1-associated pathways unveils that 3CL proteases also inactivate the pyroptosis executioner Gasdermin D (GSDMD). Subsequently, caspase-3 and GSDME promote alternative cell pyroptosis. Finally, analysis of pyroptosis markers in plasma from COVID-19 patients with characterized severe pneumonia due to autoantibodies against, or inborn errors of, type I interferons (IFNs) highlights GSDME/caspase-3 as potential markers of disease severity. Overall, our findings identify NLRP1 as a sensor of SARS-CoV-2 infection in lung epithelia.
Original languageEnglish (US)
Pages (from-to)2385-2400.e9
JournalMolecular Cell
Issue number13
StatePublished - Jul 7 2022
Externally publishedYes

Bibliographical note

Generated from Scopus record by KAUST IRTS on 2023-02-15

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology


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