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

摘要

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 x 108 +/- 2.08 x 108 CFUs/g, p < 0.01), duodenum (2.80 x 107 +/- 1.61 x 107 CFUs/g, p < 0.01), cecum (2.50 x 108 +/- 2.05 x 108 CFUs/g, p < 0.01), and MLN (1.23 x 106 +/- 8.06 x 105 CFUs/g, p < 0.01), less IL-18 production in the muscle (8.54 x 103 +/- 1.20 x 103 pg/g, p < 0.01), duodenum (3.34 x 103 +/- 2.46 x 102 pg/g, p < 0.01), and cecum (3.81 x 103 +/- 5.29 x 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.