GPR120 promotes neutrophil control of intestinal bacterial infection
ABSTRACTG-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 sequencin...
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Format: | Article |
Language: | English |
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Taylor & Francis Group
2023-12-01
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Series: | Gut Microbes |
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Online Access: | https://www.tandfonline.com/doi/10.1080/19490976.2023.2190311 |
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author | 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 |
author_facet | 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 |
author_sort | Zheng Zhou |
collection | DOAJ |
description | ABSTRACTG-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. |
first_indexed | 2024-03-11T14:19:15Z |
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institution | Directory Open Access Journal |
issn | 1949-0976 1949-0984 |
language | English |
last_indexed | 2024-04-24T17:07:14Z |
publishDate | 2023-12-01 |
publisher | Taylor & Francis Group |
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series | Gut Microbes |
spelling | doaj.art-5edc11f5c581405fb622b83cd839ccf52024-03-28T22:38:21ZengTaylor & Francis GroupGut Microbes1949-09761949-09842023-12-0115110.1080/19490976.2023.2190311GPR120 promotes neutrophil control of intestinal bacterial infectionZheng Zhou0Wenjing Yang1Tianming Yu2Yu Yu3Xiaojing Zhao4Yanbo Yu5Chuncai Gu6Anthony J Bilotta7Suxia Yao8Qihong Zhao9George Golovko10Mingsong Li11Yingzi Cong12Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, USADepartment of Microbiology and Immunology, University of Texas Medical Branch, Galveston, USADepartment of Microbiology and Immunology, University of Texas Medical Branch, Galveston, USADepartment of Microbiology and Immunology, University of Texas Medical Branch, Galveston, USADepartment of Microbiology and Immunology, University of Texas Medical Branch, Galveston, USADepartment of Microbiology and Immunology, University of Texas Medical Branch, Galveston, USADepartment of Gastroenterology, Nan Fang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Microbiology and Immunology, University of Texas Medical Branch, Galveston, USADepartment of Microbiology and Immunology, University of Texas Medical Branch, Galveston, USABristol-MyersSquibb, Princeton, New Jersey, USADepartment of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, USADepartment of Gastroenterology, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaDepartment of Microbiology and Immunology, University of Texas Medical Branch, Galveston, USAABSTRACTG-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.https://www.tandfonline.com/doi/10.1080/19490976.2023.2190311NeutrophilGPR120gut microbiotaInteric infectionIntestinal inflammation |
spellingShingle | 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 GPR120 promotes neutrophil control of intestinal bacterial infection Gut Microbes Neutrophil GPR120 gut microbiota Interic infection Intestinal inflammation |
title | GPR120 promotes neutrophil control of intestinal bacterial infection |
title_full | GPR120 promotes neutrophil control of intestinal bacterial infection |
title_fullStr | GPR120 promotes neutrophil control of intestinal bacterial infection |
title_full_unstemmed | GPR120 promotes neutrophil control of intestinal bacterial infection |
title_short | GPR120 promotes neutrophil control of intestinal bacterial infection |
title_sort | gpr120 promotes neutrophil control of intestinal bacterial infection |
topic | Neutrophil GPR120 gut microbiota Interic infection Intestinal inflammation |
url | https://www.tandfonline.com/doi/10.1080/19490976.2023.2190311 |
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