Inflammasomes are activated in response to SARS-CoV-2 infection and are associated with COVID-19 severity in patients

Severe cases of COVID-19 are characterized by a strong inflammatory process that may ultimately lead to organ failure and patient death. The NLRP3 inflammasome is a molecular platform that promotes inflammation via cleavage and activation of key inflammatory molecules including active caspase-1 (Cas...

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Vydáno v:	The Journal of experimental medicine Ročník 218; číslo 3
Hlavní autoři:	Rodrigues, Tamara S, de Sá, Keyla S G, Ishimoto, Adriene Y, Becerra, Amanda, Oliveira, Samuel, Almeida, Leticia, Gonçalves, Augusto V, Perucello, Debora B, Andrade, Warrison A, Castro, Ricardo, Veras, Flavio P, Toller-Kawahisa, Juliana E, Nascimento, Daniele C, de Lima, Mikhael H F, Silva, Camila M S, Caetite, Diego B, Martins, Ronaldo B, Castro, Italo A, Pontelli, Marjorie C, de Barros, Fabio C, do Amaral, Natália B, Giannini, Marcela C, Bonjorno, Letícia P, Lopes, Maria Isabel F, Santana, Rodrigo C, Vilar, Fernando C, Auxiliadora-Martins, Maria, Luppino-Assad, Rodrigo, de Almeida, Sergio C L, de Oliveira, Fabiola R, Batah, Sabrina S, Siyuan, Li, Benatti, Maira N, Cunha, Thiago M, Alves-Filho, José C, Cunha, Fernando Q, Cunha, Larissa D, Frantz, Fabiani G, Kohlsdorf, Tiana, Fabro, Alexandre T, Arruda, Eurico, de Oliveira, Renê D R, Louzada-Junior, Paulo, Zamboni, Dario S
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States 01.03.2021
Témata:	Apoptosis Comorbidity COVID-19 - pathology COVID-19 - virology Cytokines - biosynthesis Humans Inflammasomes - metabolism Lung - pathology Monocytes - metabolism NLR Family, Pyrin Domain-Containing 3 Protein - metabolism Postmortem Changes SARS-CoV-2 - physiology Severity of Illness Index Treatment Outcome
ISSN:	1540-9538, 1540-9538
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Shrnutí:	Severe cases of COVID-19 are characterized by a strong inflammatory process that may ultimately lead to organ failure and patient death. The NLRP3 inflammasome is a molecular platform that promotes inflammation via cleavage and activation of key inflammatory molecules including active caspase-1 (Casp1p20), IL-1β, and IL-18. Although participation of the inflammasome in COVID-19 has been highly speculated, the inflammasome activation and participation in the outcome of the disease are unknown. Here we demonstrate that the NLRP3 inflammasome is activated in response to SARS-CoV-2 infection and is active in COVID-19 patients. Studying moderate and severe COVID-19 patients, we found active NLRP3 inflammasome in PBMCs and tissues of postmortem patients upon autopsy. Inflammasome-derived products such as Casp1p20 and IL-18 in the sera correlated with the markers of COVID-19 severity, including IL-6 and LDH. Moreover, higher levels of IL-18 and Casp1p20 are associated with disease severity and poor clinical outcome. Our results suggest that inflammasomes participate in the pathophysiology of the disease, indicating that these platforms might be a marker of disease severity and a potential therapeutic target for COVID-19.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1540-9538 1540-9538
DOI:	10.1084/jem.20201707