Intestinal microbiota regulates tryptophan metabolism following oral infection with Toxoplasma gondii

Abstract

The intestinal microbiota plays an important role in modulating host immune responses. Oral Toxop/asma gondii infection can promote intestinal inflam­mation in certain mice strains. The 1DO-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.