Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, USA.
Department of Gastroenterology, Nan Fang Hospital, Southern Medical University, Guangzhou, China.
Gut Microbes. 2023 Jan-Dec;15(1):2190311. doi: 10.1080/19490976.2023.2190311.
G-protein coupled receptor 120 (GPR 120) has been implicated in anti-inflammatory functions. However, how GPR120 regulates the neutrophil function remains unknown. This study investigated the role of GPR120 in the regulation of neutrophil function against enteric bacteria. 16S rRNA sequencing was used for measuring the gut microbiota of wild-type (WT) mice and mice. infection and dextran sulfate sodium (DSS)-induced colitis models were performed in WT and mice. Mouse peritoneal-derived primary neutrophils were used to determine the neutrophil functions. mice showed altered microbiota composition. mice exhibited less capacity to clear intestinal and more severe intestinal inflammation upon infection or DSS insults. Depletion of neutrophils decreased the intestinal clearance of . GPR120 agonist, CpdA, enhanced WT neutrophil production of reactive oxygen species (ROS) and extracellular traps (NETs), and GPR120-deficient neutrophils demonstrated a lower level of ROS and NETs. CpdA-treated neutrophils showed an enhanced capacity to inhibit the growth of , which was abrogated by the inhibition of either NETs or ROS. CpdA promoted neutrophil inhibition of the growth of commensal bacteria O9:H4 and pathobiont O83:H1 isolated from a Crohn's disease patient. Mechanically, mTOR activation and glycolysis mediated GPR120 induction of ROS and NETs in neutrophils. Additionally, CpdA promoted the neutrophil production of IL-17 and IL-22, and treatment with a conditioned medium of GPR120-activated neutrophils increased intestinal epithelial cell barrier functions. Our study demonstrated the critical role of GPR120 in neutrophils in protection against enteric bacterial invasion.
G 蛋白偶联受体 120（GPR120）已被牵连到抗炎功能中。然而，GPR120 如何调节中性粒细胞功能仍不清楚。本研究调查了 GPR120 在调节中性粒细胞对抗肠道细菌功能中的作用。使用 16S rRNA 测序来测量野生型（WT）小鼠和 小鼠的肠道微生物群。在 WT 和 小鼠中进行了 感染和葡聚糖硫酸钠（DSS）诱导的结肠炎模型。使用小鼠腹膜衍生的原代中性粒细胞来确定中性粒细胞功能。 小鼠表现出改变的微生物群落组成。 小鼠在感染或 DSS 损伤时清除肠道 的能力降低，并且肠道炎症更严重。中性粒细胞耗竭减少了肠道对 的清除。GPR120 激动剂 CpdA 增强了 WT 中性粒细胞活性氧（ROS）和细胞外陷阱（NETs）的产生，而 GPR120 缺陷型中性粒细胞显示出较低水平的 ROS 和 NETs。用 CpdA 处理的中性粒细胞显示出增强抑制 的生长的能力，这一能力被 NETs 或 ROS 的抑制所阻断。CpdA 促进中性粒细胞抑制从克罗恩病患者分离的共生菌 O9:H4 和条件致病菌 O83:H1 的生长。在机制上，mTOR 激活和糖酵解介导 GPR120 诱导中性粒细胞中的 ROS 和 NETs。此外，CpdA 促进中性粒细胞产生 IL-17 和 IL-22，并且用 GPR120 激活的中性粒细胞的条件培养基处理增加了肠道上皮细胞屏障功能。本研究表明 GPR120 在中性粒细胞中对保护免受肠道细菌入侵具有关键作用。
