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

Author(s):Show less -

Rodrigues, Tamara S. ^[1] ; de Sa, Keyla S. G. ^[1] ; Ishimoto, Adriene Y. ^[1] ; Becerra, Amanda ^[1] ; Oliveira, Samuel ^[1] ; Almeida, Leticia ^{[1, 2]} ; Goncalves, V, Augusto ; Perucello, Debora B. ^[3] ; Andrade, Warrison A. ^[3] ; Castro, Ricardo ^[4] ; Veras, Flavio P. ^[5] ; Toller-Kawahisa, Juliana E. ^[5] ; Nascimento, Daniele C. ^[5] ; de Lima, Mikhael H. F. ^[5] ; Silva, Camila M. S. ^[5] ; Caetite, Diego B. ^[5] ; Martins, Ronaldo B. ^[3] ; Castro, Italo A. ^[3] ; Pontelli, Marjorie C. ^[3] ; de Barros, Fabio C. ^{[6, 7]} ; do Amaral, Natalia B. ^{[8, 9]} ; Giannini, Marcela C. ^{[8, 9]} ; Bonjorno, Leticia P. ^{[8, 9]} ; Lopes, Maria Isabel F. ^{[8, 9]} ; Santana, Rodrigo C. ^{[8, 9]} ; Vilar, Fernando C. ^{[8, 9]} ; Auxiliadora-Martins, Maria ^[10] ; Luppino-Assad, Rodrigo ^{[8, 9]} ; de Almeida, Sergio C. L. ^{[8, 9]} ; de Oliveira, Fabiola R. ^{[8, 9]} ; Batah, Sabrina S. ^[11] ; Siyuan, Li ; Benatti, Maira N. ^[12] ; Cunha, Thiago M. ^{[5, 2]} ; Alves-Filho, Jose C. ^{[5, 2]} ; Cunha, Fernando Q. ^{[5, 2]} ; Cunha, Larissa D. ^[3] ; Frantz, Fabiani G. ^[4] ; Kohlsdorf, Tiana ^[6] ; Fabro, Alexandre T. ^[12] ; Arruda, Eurico ^[3] ; de Oliveira, Rene D. R. ^{[8, 9]} ; Louzada-Junior, Paulo ^{[8, 9]} ; Zamboni, Dario S. ^{[2, 3]}

Affiliation:Show less -

^[1] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Biol Celular & Mol & Bioagentes Patogen, Ribeirao Preto - Brazil

^[2] Univ Sao Paulo, Fac Med Ribeirao Preto, Ctr Res Inflammatory Dis, Ribeirao Preto - Brazil

^[3] Goncalves, Augusto, V, Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Biol Celular & Mol & Bioagentes Patogen, Ribeirao Preto - Brazil

^[4] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Dept Analises Clin Toxicol & Bromatol, Ribeirao Preto - Brazil

^[5] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Farmacol, Ribeirao Preto - Brazil

^[6] Univ Sao Paulo, Fac Filosofia Ciencias & Letras Ribeirao Preto, Dept Biol, Ribeirao Preto - Brazil

^[7] Univ Fed Sao Paulo, Inst Ciencias Ambientais Quim & Farmaceut, Dept Ecol & Biol Evolut, Diadema - Brazil

^[8] Univ Sao Paulo, Fac Med Ribeirao Preto, Div Imunol Clin Doencas Infecciosas, Ribeirao Preto - Brazil

^[9] Univ Sao Paulo, Fac Med Ribeirao Preto, Unidade Terapia Intens, Ribeirao Preto - Brazil

^[10] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Cirurgia & Anat, Div Med Intens, Ribeirao Preto - Brazil

^[11] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Patol & Med Legal, Ribeirao Preto - Brazil

^[12] Li Siyuan, Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Patol & Med Legal, Ribeirao Preto - Brazil

• Document type: Journal article
• Source: JOURNAL OF EXPERIMENTAL MEDICINE; v. 218, n. 3 MAR 1 2021.
• Web of Science Citations: 52

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-1 beta, 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. (AU)

• FAPESP's process: 20/04964-8 - Inflammasome activation by SARS-CoV-2 and the role of this platform in the pathogenesis of COVID-19: a prospective study aiming at NLRP3 inhibition for COVID-19 treatment
• Grantee: Dario Simões Zamboni
• Support Opportunities: Regular Research Grants
• FAPESP's process: 13/08216-2 - CRID - Center for Research in Inflammatory Diseases
• Grantee: Fernando de Queiroz Cunha
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 19/11342-6 - Mechanisms and consequences of the activation of cytoplasmic receptors by intracellular pathogens
• Grantee: Dario Simões Zamboni
• Support Opportunities: Research Projects - Thematic Grants