G 蛋白偶联受体 120 通过调节 NOD 样受体家族含 pyrin 域蛋白 3 炎性小体激活来介导宿主抗感染防御。

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

机构信息

State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, College of Life Sciences, Inner Mongolia University, Hohhot 010070, China.

Animal Husbandry Institute, Agriculture and Animal Husbandry Academy of Inner Mongolia, Hohhot 010031, China.

出版信息

J Agric Food Chem. 2023 May 10;71(18):7119-7130. doi: 10.1021/acs.jafc.3c01242. Epub 2023 Apr 28.

DOI:10.1021/acs.jafc.3c01242

PMID:37115810

Abstract

is a major cause of infectious foodborne disease, frequently associated with the consumption of raw and undercooked food. Despite intensive studies on clarifying pathogenesis, the molecular mechanisms of host-pathogen interactions remain poorly understood. In soft tissue and mucosal infection models, mice, G protein-coupled receptor 120 (GPR120), are more susceptible to infection. deficiency leads to a low survival rate (30 and 10%, < 0.01), more bacterial loads in the muscle (2.26 × 10 ± 2.08 × 10 CFUs/g, < 0.01), duodenum (2.80 × 10 ± 1.61 × 10 CFUs/g, < 0.01), cecum (2.50 × 10 ± 2.05 × 10 CFUs/g, < 0.01), and MLN (1.23 × 10 ± 8.06 × 10 CFUs/g, < 0.01), less IL-18 production in the muscle (8.54 × 10 ± 1.20 × 10 pg/g, < 0.01), duodenum (3.34 × 10 ± 2.46 × 10 pg/g, < 0.01), and cecum (3.81 × 10 ± 5.29 × 10 pg/g, < 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.

摘要

是食源性传染病的主要病因，常与生食和未煮熟的食物有关。尽管对发病机制进行了深入研究，但宿主-病原体相互作用的分子机制仍知之甚少。在软组织和黏膜感染模型中，G 蛋白偶联受体 120（GPR120）更容易感染。缺乏会导致存活率低（30%和 10%，<0.01），肌肉中的细菌负荷更高（2.26×10±2.08×10 CFUs/g，<0.01），十二指肠（2.80×10±1.61×10 CFUs/g，<0.01），盲肠（2.50×10±2.05×10 CFUs/g，<0.01），和 MLN（1.23×10±8.06×10 CFUs/g，<0.01），肌肉中 IL-18 产生减少（8.54×10±1.20×10 pg/g，<0.01），十二指肠（3.34×10±2.46×10 pg/g，<0.01），盲肠（3.81×10±5.29×10 pg/g，<0.01），以及严重的器官损伤。显然，GPR120 通过钾外流依赖的 NOD 样受体家族 pyrin 结构域包含 3（NLRP3）信号促进 IL-18 的产生和病原体的控制。从机制上讲，GPR120 与 NLRP3 的相互作用增强了 NLRP3 炎性小体的组装。因此，本研究揭示了 GPR120 在宿主保护中的新作用，并表明 GPR120 可能是限制病原体感染的潜在治疗靶点。