Intestinal microbiota regulates tryptophan metabolism following oral infection with Toxoplasma gondii

Parasite Immunol. 2020 Sep;42(9):e12720. doi: 10.1111/pim.12720. Epub 2020 May 3.

Abstract

Introduction: The intestinal microbiota plays an important role in modulating host immune responses. Oral Toxoplasma gondii infection can promote intestinal inflammation in certain mice strains. The IDO-AhR axis may control tryptophan (Trp) metabolism constituting an important immune regulatory mechanism in inflammatory settings.

Aims: In the present study, we investigated the role of the intestinal microbiota on Trp metabolism during oral infection with T gondii.

Methods and results: Mice were treated with antibiotics for four weeks and then infected with T gondii by gavage. Histopathology and immune responses were evaluated 8 days after infection. We found that depletion of intestinal microbiota by antibiotics contributed to resistance against T gondii infection and led to reduced expression of AhR on dendritic and Treg cells. Mice depleted of Gram-negative bacteria presented higher levels of systemic Trp, downregulation of AhR expression and increased resistance to infection whereas depletion of Gram-positive bacteria did not affect susceptibility or expression of AhR on immune cells.

Conclusion: Our findings indicate that the intestinal microbiota can control Trp availability and provide a link between the AhR pathway and host-microbiota interaction in acute infection with T gondii.

Keywords: Toxoplasma gondii; antibiotics; intestinal inflammation; microbiota; tryptophan.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Female
  • Gastrointestinal Microbiome / physiology*
  • Inflammation / immunology
  • Mice
  • Mice, Inbred C57BL
  • Toxoplasma / immunology
  • Toxoplasmosis / immunology
  • Toxoplasmosis / metabolism*
  • Tryptophan / metabolism*

Substances

  • Tryptophan