Caspase-11 Mediated Hyperinflammation Impairs CD8⁺ T Cell Immunity and Viral Clearance in Severe SARS-CoV-2 Infection.

ABSTRACT: Severe SARS-CoV-2 infection is characterized by lung hyperinflammation, impaired interferon responses, and defective T-cell activation, yet the molecular drivers of these immune dysregulations remain incompletely understood. Caspase-11 (CASP11), a key mediator of the non-canonical inflammasome, has been shown to mediate an innate hyperinflammatory response and cytokine release in a non-severe, non-lethal SARS-CoV-2 infection model. However, the role played by CASP11 in severe SARS-CoV-2 disease and how it impacts adaptive immunity is not identified. Here, we newly discover that CASP11 exacerbates severe SARS-CoV-2 pathogenesis by amplifying early innate immune responses while concurrently impairing antiviral CD8 T-cell immunity. Using global knockouts, reciprocal bone marrow chimeras, and

SUBMITTER: Eltobgy MM 

PROVIDER: S-EPMC12637614 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature