G Protein-Coupled Receptor 120 Mediates Host Defense against Clostridium perfringens Infection through Regulating NOD-like Receptor Family Pyrin Domain-Containing 3 Inflammasome Activation

Clostridium perfringens is a major cause of infectious foodborne disease, frequently associated with the consumption of raw and undercooked food. Despite intensive studies on clarifying C. perfringens pathogenesis, the molecular mechanisms of host–pathogen interactions remain poorly understood. In soft tissue and mucosal infection models, Gpr120^‑/‑ mice, G protein-coupled receptor 120 (GPR120), are more susceptible to C. perfringens infection. Gpr120 deficiency leads to a low survival rate (30 and 10%, p < 0.01), more bacterial loads in the muscle (2.26 × 10⁸ ± 2.08 × 10⁸ CFUs/g, p < 0.01), duodenum (2.80 × 10⁷ ± 1.61 × 10⁷ CFUs/g, p < 0.01), cecum (2.50 × 10⁸ ± 2.05 × 10⁸ CFUs/g, p < 0.01), and MLN (1.23 × 10⁶ ± 8.06 × 10⁵ CFUs/g, p < 0.01), less IL-18 production in the muscle (8.54 × 10³ ± 1.20 × 10³ pg/g, p < 0.01), duodenum (3.34 × 10³ ± 2.46 × 10² pg/g, p < 0.01), and cecum (3.81 × 10³ ± 5.29 × 10² pg/g, p < 0.01), and severe organ injury. Obviously, GPR120 facilitates IL-18 production and pathogen control via potassium efflux-dependent NOD-like receptor family pyrin domain-containing 3 (NLRP3) signaling. Mechanistically, GPR120 interaction with NLRP3 potentiates the NLRP3 inflammasome assembly. Thus, this study uncovers a novel role of GPR120 in host protection and reveals that GPR120 may be a potential therapeutic target for limiting pathogen infection.