학술논문
CASP4/11 Contributes to NLRP3 Activation and COVID-19 Exacerbation.
Document Type
Article
Author
Rodrigues, Tamara S; Caetano, Camila C S; Sá, Keyla S G de; Almeida, Leticia; Becerra, Amanda; Gonçalves, Augusto V; Lopes, Leticia de Sousa; Oliveira, Samuel; Mascarenhas, Danielle P A; Batah, Sabrina S; Silva, Bruna M; Gomes, Giovanni F; Castro, Ricardo; Martins, Ronaldo B; Avila, Jonathan; Frantz, Fabiani G; Cunha, Thiago M; Arruda, Eurico; Cunha, Fernando Q; Nakaya, Helder
Source
Subject
*SARS-CoV-2
*NLRP3 protein
*CORONAVIRUS diseases
*COVID-19
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Language
ISSN
0022-1899
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection triggers activation of the NLRP3 inflammasome, which promotes inflammation and aggravates severe COVID-19. Here, we report that SARS-CoV-2 induces upregulation and activation of human caspase-4/CASP4 (mouse caspase-11/CASP11), and this process contributes to NLRP3 activation. In vivo infections performed in transgenic hACE2 humanized mice, deficient or sufficient for Casp11 , indicate that hACE2 Casp11−/− mice were protected from disease development, with the increased pulmonary parenchymal area, reduced clinical score of the disease, and reduced mortality. Assessing human samples from fatal cases of COVID-19, we found that CASP4 was expressed in patient lungs and correlated with the expression of inflammasome components and inflammatory mediators, including CASP1 , IL1B , IL18, and IL6. Collectively, our data establish that CASP4/11 promotes NLRP3 activation and disease pathology, revealing a possible target for therapeutic interventions for COVID-19. [ABSTRACT FROM AUTHOR]