Participation of kynurenine pathway metabolites in Trypanosoma cruzi infection of human placenta.

INTRODUCTION

The kynurenine pathway is a major route of tryptophan (Trp) metabolism, an essential amino acid. This pathway, mediated by Indoleamine 2,3-dioxygenase (IDO), contributes to maternal-fetal tolerance by depletion Trp and generating kynurenines (Kyn). Among the Kyns produced in the placenta, 3-hydroxykynurenine (3-HK) and 3-hydroxy-anthranilic acid (3-HAA) have been shown to affect T. cruzi replication. This study aimed to evaluate the role of kynurenine pathway metabolites in Trypanosoma cruzi (T. cruzi) infection of the human placenta.

METHODS

Term human placental explants (n = 8) were infected with 105 T. cruzi trypomastigotes/mL for 24 h. The explants were treated with L-Trp, L-1-methyl-tryptophan (L-1MT), IFN-γ, 3-HK and 3-HAA for 72 or 96 hpi. IDO expression was assessed by immunohistochemistry, and IDO activity was measured in homogenates. L-Kyn concentration was quantified in culture supernatants, while infection levels were determined by qPCR. Statistical analysis included ANOVA with Tukey's post hoc test and Student's t-test (p < 0.05).

RESULTS

L-Trp increased IDO expression and activity, elevating L-Kyn production in both infected and non-infected explants. L-1MT reduced L-Kyn production, whereas IFN-γ stimulated it. Additionally, 3-HK significantly impaired trypomastigotes motility. Both 3-HK and 3-HAA decreased placenta explant infection by T. cruzi.

CONCLUSION

Metabolites of the kynurenine pathways reduced T. cruzi infection in placental explants, suggesting a potential role in limiting congenital transmission of Chagas disease by modulating parasitic load in human placenta.