ABSTRACT
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.