Inflammasomes are activated in response to SARS-CoV-2 infection and are associated with COVID-19 severity in patients-Reference-Cited by-同舟云学术

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

Published:2020-11-24 Issue:3 Volume:218 Page:
ISSN:0022-1007
Container-title:Journal of Experimental Medicine
language:en
Short-container-title:

Author:

Rodrigues Tamara S.¹^ORCID,de Sá Keyla S.G.¹^ORCID,Ishimoto Adriene Y.¹^ORCID,Becerra Amanda¹^ORCID,Oliveira Samuel¹^ORCID,Almeida Leticia¹²^ORCID,Gonçalves Augusto V.¹^ORCID,Perucello Debora B.¹^ORCID,Andrade Warrison A.¹^ORCID,Castro Ricardo³^ORCID,Veras Flavio P.⁴^ORCID,Toller-Kawahisa Juliana E.⁴^ORCID,Nascimento Daniele C.⁴^ORCID,de Lima Mikhael H.F.⁴^ORCID,Silva Camila M.S.⁴^ORCID,Caetite Diego B.⁴^ORCID,Martins Ronaldo B.¹^ORCID,Castro Italo A.¹^ORCID,Pontelli Marjorie C.¹^ORCID,de Barros Fabio C.⁵⁶^ORCID,do Amaral Natália B.⁷^ORCID,Giannini Marcela C.⁷^ORCID,Bonjorno Letícia P.⁷^ORCID,Lopes Maria Isabel F.⁷^ORCID,Santana Rodrigo C.⁷^ORCID,Vilar Fernando C.⁷^ORCID,Auxiliadora-Martins Maria⁸^ORCID,Luppino-Assad Rodrigo⁷^ORCID,de Almeida Sergio C.L.⁷^ORCID,de Oliveira Fabiola R.⁷^ORCID,Batah Sabrina S.⁹^ORCID,Siyuan Li⁹^ORCID,Benatti Maira N.⁹^ORCID,Cunha Thiago M.²⁴^ORCID,Alves-Filho José C.²⁴^ORCID,Cunha Fernando Q.²⁴^ORCID,Cunha Larissa D.¹^ORCID,Frantz Fabiani G.³^ORCID,Kohlsdorf Tiana⁵^ORCID,Fabro Alexandre T.⁹^ORCID,Arruda Eurico¹^ORCID,de Oliveira Renê D.R.⁷^ORCID,Louzada-Junior Paulo⁷^ORCID,Zamboni Dario S.¹²^ORCID

Affiliation:

1. Departamento de Biologia Celular e Molecular e Bioagentes Patogênicos, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil

2. Center of Research in Inflammatory Diseases, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil

3. Departamento de Análises Clínicas, Toxicológicas e Bromatologia, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil

4. Departamento de Farmacologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil

5. Departamento de Biologia, Faculdade de Filosofia Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil

6. Departamento de Ecologia e Biologia Evolutiva, Instituto de Ciências Ambientais, Químicas e Farmacêuticas, Universidade Federal de São Paulo, Diadema, Brazil

7. Divisão de Imunologia Clinica, Emergência, Doenças Infecciosas e Unidade de Terapia Intensiva, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil

8. Divisão de Medicina Intensiva, Departamento de Cirurgia e Anatomia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil

9. Departamento de Patologia e Medicina Legal, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil

Abstract

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.

Funder

Fundação de Amparo à Pesquisa do Estado de São Paulo

Conselho Nacional de Desenvolvimento Científico e Tecnológico

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior

Center for Research in Inflammatory Disease

Instituto Nacional de Ciência e Tecnologia de Vacinas

Publisher

Rockefeller University Press

Subject

Immunology,Immunology and Allergy

Link

http://rupress.org/jem/article-pdf/doi/10.1084/jem.20201707/1414791/jem_20201707.pdf