Mary Wilson
Well-known member
Published: 10 February 2023
https://doi.org/10.1093/infdis/jiad037
Tamara S Rodrigues, Camila C S Caetano, Keyla S G de Sá, Leticia Almeida, Amanda Becerra, Augusto V Gonçalves, Leticia de Sousa Lopes, Samuel Oliveira, Danielle P A Mascarenhas, Sabrina S Batah, Bruna M Silva, Giovanni F Gomes, Ricardo Castro, Ronaldo B Martins, Jonathan Avila, Fabiani G Frantz, Thiago M Cunha, Eurico Arruda, Fernando Q Cunha, Helder Nakaya, Larissa D Cunha, Alexandre T Fabro, Paulo Louzada-Junior, Renê D R de Oliveira, Dario S Zamboni
Abstract
The SARS-CoV-2 infection triggers activation of the NLRP3 inflammasome, which promotes inflammation and aggravates the severe cases of COVID-19. Here, we reported 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 vivoinfections performed in transgenic hACE2 humanized mice, deficient or sufficient for Casp11, indicate that hACE2 Casp11[SUP]–/–[/SUP]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 to COVID-19.
https://watermark.silverchair.com/j...DDAhICXvHXiA3fmcESHXlC7rTcpPa9T4foj4UNALBD_m1
https://doi.org/10.1093/infdis/jiad037
Tamara S Rodrigues, Camila C S Caetano, Keyla S G de Sá, Leticia Almeida, Amanda Becerra, Augusto V Gonçalves, Leticia de Sousa Lopes, Samuel Oliveira, Danielle P A Mascarenhas, Sabrina S Batah, Bruna M Silva, Giovanni F Gomes, Ricardo Castro, Ronaldo B Martins, Jonathan Avila, Fabiani G Frantz, Thiago M Cunha, Eurico Arruda, Fernando Q Cunha, Helder Nakaya, Larissa D Cunha, Alexandre T Fabro, Paulo Louzada-Junior, Renê D R de Oliveira, Dario S Zamboni
Abstract
The SARS-CoV-2 infection triggers activation of the NLRP3 inflammasome, which promotes inflammation and aggravates the severe cases of COVID-19. Here, we reported 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 vivoinfections performed in transgenic hACE2 humanized mice, deficient or sufficient for Casp11, indicate that hACE2 Casp11[SUP]–/–[/SUP]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 to COVID-19.
https://watermark.silverchair.com/j...DDAhICXvHXiA3fmcESHXlC7rTcpPa9T4foj4UNALBD_m1