NLRC4 inhibits NLRP3 inflammasome and abrogates effective antifungal CD8⁺ T cell responses.

ABSTRACT: The recognition of fungi by intracellular NOD-like receptors (NLRs) induces inflammasome assembly and activation. Although the NLRC4 inflammasome has been extensively studied in bacterial infections, its role during fungal infections is unclear. Paracoccidioidomycosis (PCM) is a pathogenic fungal disease caused by Paracoccidioides brasiliensis. Here, we show that NLRC4 confers susceptibility to experimental PCM by regulating NLRP3-dependent cytokine production and thus protective effector mechanisms. Early after infection, NLRC4 suppresses prostaglandin E₂ production, and consequently reduces interleukin (IL)-1β release by macrophages and dendritic cells in the lungs. IL-1β is required to control fungal replication via induction of the nitric oxide synthase 2 (NOS2) pathw

SUBMITTER: Souza COS 

PROVIDER: S-EPMC8184506 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature