2. Academic Validation
  3. Edwardsiella piscicida infection-induced tryptophan-kynurenine metabolic pathway impairs Th17 cells to drive intestinal inflammation in teleost

Edwardsiella piscicida infection-induced tryptophan-kynurenine metabolic pathway impairs Th17 cells to drive intestinal inflammation in teleost

  • Fish Shellfish Immunol. 2025 Aug:163:110425. doi: 10.1016/j.fsi.2025.110425.
Jin Yang 1,  Qian Wang 1,  Zhuang Wang 1,  Yuanxing Zhang 2,  Qin Liu 3,  Dahai Yang 4
Affiliations

Affiliations

  • 1 State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, China.
  • 2 State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, China; Laboratory for Aquatic Animal Diseases of MOA, Shanghai, 201400, China.
  • 3 State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, China; Laboratory for Aquatic Animal Diseases of MOA, Shanghai, 201400, China; Shanghai Engineering Research Center of Maricultured Animal Vaccines, Shanghai, 200237, China.
  • 4 State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, China; Laboratory for Aquatic Animal Diseases of MOA, Shanghai, 201400, China; Shanghai Engineering Research Center of Maricultured Animal Vaccines, Shanghai, 200237, China. Electronic address: dahaiyang@ecust.edu.cn.
PMID: 40383498 DOI: 10.1016/j.fsi.2025.110425
Abstract

Enteric pathogens exacerbate intestinal inflammation by disrupting microbiota-host metabolic interactions. While T helper 17 (Th17) cells are critical for maintaining intestinal homeostasis, the mechanisms through which enteric pathogens manipulate the function of Th17 cells to drive inflammation remain poorly understood. In this study, we established an immersion Infection model using Edwardsiella piscicida in turbot (Scophthalmus maximus) to investigate the mechanism about enteric pathogen-induced intestinal inflammation, and found that E. piscicida Infection significantly impairs the function of intestinal Th17 cells. By analyzing changes in the intestinal microbiota and metabolites, we observed a marked increase in the abundance of Proteobacteria phylum, which positively correlated with elevated levels of tryptophan-kynurenine (Trp-Kyn) pathway metabolites. Further investigation revealed that the enhanced Trp-Kyn pathway inhibits the function of intestinal Th17 cells. Importantly, pharmacological inhibition of the Trp-Kyn pathway could restore the function of Th17 cells and alleviate the infection-induced intestinal inflammation. Taken together, these findings uncover a critical link between microbiota-mediated tryptophan metabolism and Th17 cell's dysregulation during enteric pathogen Infection in teleost, which provide novel insights into the metabolic reprogramming of host immunity and to identify potential therapeutic targets for mitigating intestinal inflammation.

Keywords

Edwardsiella piscicida; Intestinal inflammation; Microbiota; Th17 cells; Tryptophan-kynurenine pathway; Turbot.

Figures
Products