The Trypanosome-Derived Metabolite Indole-3-Pyruvate Inhibits Prostaglandin Production in Macrophages by Targeting COX2

Abstract The protozoan parasite Trypanosoma brucei is the causative agent of neglected tropical disease human African trypanosomiasis, otherwise known as sleeping sickness. Trypanosomes have evolved many immune-evasion mechanisms to facilitate their own survival, well prolonging host survival ensure completion parasitic life cycle. A key feature bloodstream form T. secretion aromatic keto acids, which are metabolized from tryptophan. In this study, we describe an immunomodulatory role for one these indole-3-pyruvate (I3P). We demonstrate that I3P inhibits production PGs in activated macrophages. also show that, despite reduction downstream PGs, augments expression cyclooxygenase (COX2). This increase COX2 mediated part via inhibition relieving a negative-feedback loop on COX2. Activation aryl hydrocarbon receptor participates effect. However, little functionality, provide evidence suggest targets COX activity. study therefore details evasion strategy by trypanosome-secreted metabolite potently macrophage-derived might promote and trypanosome survival.