Indoleamine 2,3-Dioxygenase and Tryptophan Catabolism: Key Players in Immunosuppression and Intracellular Parasite Survival Mechanisms

Indoleamine 2,3-dioxygenase (IDO) is a heme enzyme that catalyzes the oxidative degradation of L-tryptophan (L-Trp) through the kynurenine pathway (KP), generating metabolites that regulate immune responses. These byproducts, mainly kynurenines, contribute to immunosuppression and influence immune cell differentiation, promoting regulatory T cells (Tregs) and inducing apoptosis in inflammatory cells. We conducted a comprehensive literature review to examine the roles of IDO and KP metabolites in intracellular parasitic infections. Our analysis focused on studies involving Leishmania, Trypanosoma cruzi, Toxoplasma gondii, and Plasmodium species. IDO has a dual role in parasitic diseases: L-Trp depletion can inhibit parasite growth, but also promotes an immunosuppressive microenvironment that may facilitate pathogen persistence. This balance between host defense and immune evasion is crucial in chronic infections. We discuss how IDO activity intersects with parasite immune evasion strategies and review potential therapeutic approaches targeting the IDO-KP axis. IDO plays a complex and context-dependent role in the immunopathology of intracellular parasitic infections. While it may support host defense, its immunoregulatory effects can also favor chronic infection. Therapeutically targeting the IDO pathway is a promising strategy, but requires further investigation to optimize its clinical application.