NLRC4, also known as NLR-family CARD-containing protein 4, is a key component of the inflammasome, a cytosolic multiprotein complex. It plays a crucial role in the innate immune response, sensing microbial infections or host cell damage, and triggering cytokine production and pyroptosis, a pro-inflammatory form of cell death [2,3]. The NLRC4 inflammasome is involved in pathways related to the restriction of bacterial infections, and its dysregulation can lead to autoinflammatory diseases [2,3]. Genetic models, such as gene knockout (KO) or conditional knockout (CKO) mouse models, are valuable tools for studying NLRC4's functions.

SIRT3-deficient KO mouse models have shown that SIRT3-mediated deacetylation of NLRC4 is pivotal for NLRC4 inflammasome activation and pyroptosis both in vitro and in vivo. SIRT3 promotes NLRC4 inflammasome assembly, which is essential for the clearance of Salmonella typhimurium infection [1]. In addition, Nlrc4 -/- mice infected with herpes simplex virus-1 (HSV-1) show higher mortality, attenuated Ifn-β, Isg54, and Isg56 mRNA transcription, and TBK1 phosphorylation, indicating that NLRC4 promotes the cGAS-STING signaling pathway and antiviral innate immunity [4].

In conclusion, NLRC4 is essential for the proper functioning of the innate immune response, especially in controlling bacterial and viral infections. Studies using KO/CKO mouse models have revealed its role in inflammasome activation, pyroptosis, and antiviral signaling pathways. Understanding NLRC4's functions can potentially lead to new therapeutic strategies for autoinflammatory diseases and viral infections.