Dual Faces of γδ T-cells in Trypanosomatid infections

In this review, we tell a story of how two related parasites that belong to the same genus, Trypanosoma brucei and Trypanosoma cruzi, cause very distinct lethal diseases and how γδ T-cells help shape these outcomes. It synthesizes current knowledge on γδ T-cell responses to T. brucei and T. cruzi, highlighting shared and parasite-specific features. Here we emphasize how γδ T-cell cytotoxic versus regulatory programs and tissue residency in blood, lymphoid organs, liver, gut, heart and skin influence early parasite control, chronic persistence, and immunopathology. Finally, we discuss the gaps that need to be filled and how these insights may inform new interventions, including modulation of γδ function, γδ-targeted vaccine strategies, and γδ-based biomarkers for host-directed therapies in Chagas disease and human African trypanosomiasis.