Human NLRP1 is a sensor of pathogenic coronavirus 3CL proteases in lung epithelial cells.
Mol Cell
; 82(13): 2385-2400.e9, 2022 07 07.
Article
in English
| MEDLINE | ID: covidwho-1851815
ABSTRACT
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.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Epithelial Cells
/
Inflammasomes
/
NLR Proteins
/
Coronavirus 3C Proteases
/
SARS-CoV-2
/
COVID-19
Type of study:
Prognostic study
Limits:
Humans
Language:
English
Journal:
Mol Cell
Journal subject:
Molecular Biology
Year:
2022
Document Type:
Article
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