Caspase-4/11 induces lung inflammation and dampens the humoral immune response in SARS-CoV2 infected mice 3644

Abstract Description SARS-CoV2 devastated the world in 2019, with over 774 million cases and around 7 million deaths. Our lab has previously reported the role Caspase-4/11 plays in the innate immune response against SARS-CoV2, associating it with exacerbated lung pathology and immunothrombosis, indicating its therapeutic potential. In a recent project, we investigated how Casp-11 affects the adaptive immune response. We infected C57/BL6 mice expressing or lacking Casp-11 with the mouse-adapted SARS-CoV-2 strain (MA10). We then assessed the mice for signs of severe disease, such as weight loss, and their localized and systemic immune responses, measuring virus-specific immunoglobulins, circulating or lung resident CD4+ and CD8+ T cells (Trm), and lung cytokines. Our results indicated that Casp-11-/- mice have faster recovery than wild-type mice, along with reduced proinflammatory cytokine levels, further confirming the role of Casp-11 in lung inflammation. Additionally, the number of virus-specific CD8+ Trm cells was significantly lower in Casp-11-/- mice’s lungs than in wild-type mice. However, both groups’ levels of virus-specific CD4+ Trm and lung IgGs remained comparable. Notably, Casp-11-/- mice had higher serum levels of spike-specific IgG, suggesting a potential dichotomy in the localized versus systemic immune responses. These findings indicate that targeting Casp-11 may effectively decrease disease severity while improving the acquired protective immune response. Topic Categories Viral Immunology (VIR)