Inflammasome activation by SARS-CoV-2 and its participation in COVID-19 exacerbation

COVID-19 is an infectious and inflammatory disease caused by SARS-CoV-2 (Severe Acute Respiratory Syndrome-Coronavirus-2) that might progress to severe illness in humans, characterized by excessive pulmonary and systemic inflammation. Exacerbated production of inflammatory cytokines and cell death contributes to disease aggravation and the inflammasomes take a central stage in this process. Activation of the NLRP3 has been demonstrated in macrophages and monocytes infected in vitro, in mouse models of infection, and in cells and lungs of severe cases of COVID-19. It is still not clear how SARS-CoV-2 activates the NLRP3 inflammasome, and recent reports suggest that the virus engages the CASP4/11 (Caspase 4/11)-mediated noncanonical activation of NLRP3. In this review, we discuss the recent data regarding the activation of NLRP3 inflammasome by SARS-CoV-2 and their participation in the development of severe cases of COVID-19. •SARS-CoV-2 infection in vitro triggers activation of the NLRP3 inflammasome .•The NLRP3 is activated in mice infected with SARS-CoV-2 and in the lungs of COVID-19 patients.•CASP4/11 is activated in response to infection and triggers the noncanonical NLRP3 activation.•Activation of CASP4/11 and NLRP3 contributes to disease exacerbation.