GPR120 promotes neutrophil control of intestinal bacterial infection

Zheng Zhou, Wenjing Yang, Tianming Yu, Yu Yu, Xiaojing Zhao, Yanbo Yu, Chuncai Gu, Anthony J. Bilotta, Suxia Yao, Qihong Zhao, George Golovko, Mingsong Li, Yingzi Cong

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

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 Gpr120 −/− mice. Citrobacter rodentium infection and dextran sulfate sodium (DSS)-induced colitis models were performed in WT and Gpr120 −/− mice. Mouse peritoneal-derived primary neutrophils were used to determine the neutrophil functions. Gpr120 −/− mice showed altered microbiota composition. Gpr120 −/− mice exhibited less capacity to clear intestinal Citrobacter rodentium and more severe intestinal inflammation upon infection or DSS insults. Depletion of neutrophils decreased the intestinal clearance of Citrobacter rodentium. 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 Citrobacter rodentium, which was abrogated by the inhibition of either NETs or ROS. CpdA promoted neutrophil inhibition of the growth of commensal bacteria Escherichia coli O9:H4 and pathobiont Escherichia coli 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.

Original languageEnglish (US)
Article number2190311
Pages (from-to)2190311
JournalGut Microbes
Volume15
Issue number1
DOIs
StatePublished - Dec 31 2023

Keywords

  • GPR120
  • Interic infection
  • Intestinal inflammation
  • Neutrophil
  • gut microbiota

ASJC Scopus subject areas

  • Microbiology
  • Microbiology (medical)
  • Gastroenterology
  • Infectious Diseases

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