TY - JOUR
T1 - Human NLRP1 is a sensor of pathogenic coronavirus 3CL proteases in lung epithelial cells
AU - Planès, Rémi
AU - Pinilla, Miriam
AU - Santoni, Karin
AU - Hessel, Audrey
AU - Passemar, Charlotte
AU - Lay, Kenneth
AU - Paillette, Perrine
AU - Valadão, Ana Luiza Chaves
AU - Robinson, Kim Samirah
AU - Bastard, Paul
AU - Lam, Nathaniel
AU - Fadrique, Ricardo
AU - Rossi, Ida
AU - Pericat, David
AU - Bagayoko, Salimata
AU - Leon-Icaza, Stephen Adonai
AU - Rombouts, Yoann
AU - Perouzel, Eric
AU - Tiraby, Michèle
AU - Zhang, Qian
AU - Cicuta, Pietro
AU - Jouanguy, Emmanuelle
AU - Neyrolles, Olivier
AU - Bryant, Clare E.
AU - Floto, Andres R.
AU - Goujon, Caroline
AU - Lei, Franklin Zhong
AU - Martin-Blondel, Guillaume
AU - Silva, Stein
AU - Casanova, Jean Laurent
AU - Cougoule, Céline
AU - Reversade, Bruno
AU - Marcoux, Julien
AU - Ravet, Emmanuel
AU - Meunier, Etienne
N1 - Generated from Scopus record by KAUST IRTS on 2023-02-15
PY - 2022/7/7
Y1 - 2022/7/7
N2 - 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.
AB - 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.
UR - https://linkinghub.elsevier.com/retrieve/pii/S1097276522004336
UR - http://www.scopus.com/inward/record.url?scp=85130477866&partnerID=8YFLogxK
U2 - 10.1016/j.molcel.2022.04.033
DO - 10.1016/j.molcel.2022.04.033
M3 - Article
C2 - 35594856
SN - 1097-4164
VL - 82
SP - 2385-2400.e9
JO - Molecular Cell
JF - Molecular Cell
IS - 13
ER -
