Human NLRP1 is a sensor of pathogenic coronavirus 3CL proteases in lung epithelial cells.
COVID-19
/ genetics
Caspase 3
/ metabolism
Coronavirus 3C Proteases
/ genetics
Epithelial Cells
/ metabolism
Humans
Inflammasomes
/ genetics
Lung
/ metabolism
NLR Proteins
/ genetics
Peptide Hydrolases
/ genetics
Phosphate-Binding Proteins
/ genetics
Pore Forming Cytotoxic Proteins
/ genetics
Pyroptosis
SARS-CoV-2
/ enzymology
3CL proteases
Gasdermins
NLRP1 inflammasome
SARS-CoV-2
epithelial cells
pyroptosis
Journal
Molecular cell
ISSN: 1097-4164
Titre abrégé: Mol Cell
Pays: United States
ID NLM: 9802571
Informations de publication
Date de publication:
07 07 2022
07 07 2022
Historique:
received:
19
10
2021
revised:
16
02
2022
accepted:
25
04
2022
pubmed:
21
5
2022
medline:
14
7
2022
entrez:
20
5
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 35594856
pii: S1097-2765(22)00433-6
doi: 10.1016/j.molcel.2022.04.033
pmc: PMC9108100
pii:
doi:
Substances chimiques
GSDMD protein, human
0
Inflammasomes
0
NLR Proteins
0
NLRP1 protein, human
0
Phosphate-Binding Proteins
0
Pore Forming Cytotoxic Proteins
0
Peptide Hydrolases
EC 3.4.-
3C-like protease, SARS coronavirus
EC 3.4.22.-
Caspase 3
EC 3.4.22.-
Coronavirus 3C Proteases
EC 3.4.22.28
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2385-2400.e9Informations de copyright
Copyright © 2022 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
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