Phenotypic characterization of mucosal-associated invariant T cells in visceral leishmaniasis and HIV co-infection

Abstract

Introduction Mucosal-associated invariant T (MAIT) cells are unconventional T lymphocytes with innate-like antimicrobial responsiveness. Despite their recognized role in bacterial and viral infections, their involvement in protozoal diseases, particularly visceral leishmaniasis (VL) and HIV co-infection, remains poorly understood. Methods A cross-sectional study evaluated the immunophenotypic profile of circulating MAIT cells in visceral leishmaniasis patients (VL, n = 8), VL–HIV co-infection patients (VL–HIV, n = 10), VL–HIV coinfected patients under liposomal amphotericin B prophylactic treatment (VL–HIV(T), n = 9), and reference groups comprising HIV-mono-infected (HIV, n = 11) and non-infected (NI, n = 11) individuals. Multiparameter flow cytometry assessed MAIT cell frequency, subset distribution (CD4+, CD8+ and CD4-CD8-), and the expression of activation, costimulatory, cytotoxic, exhaustion and memory markers. Integrative correlation network analysis was performed to evaluate immunological interactions among MAIT cell markers. Results MAIT cell frequencies were significantly reduced in VL and VL–HIV, predominantly affecting the CD8+ subset. Fold-change analyses demonstrated increased activation and cytotoxicity signatures in VL and VL–HIV patients, with marked upregulation of CD69, CD38, NKG2D, and CD107A, concomitant with increased expression of inhibitory receptors (PD-1, TIM-3, LAG-3), particularly in CD8+ and CD4−CD8− MAIT cells. In contrast, VL–HIV(T) patients exhibited a decrease in this hyperactivated/exhausted phenotype and partial restoration of central memory-associated features, suggesting immune rebalancing under treatment. Integrative correlation network analysis revealed marked differences of MAIT cell immunological interactions. VL and VL–HIV groups displayed reduced network density, decreased selective axis connectivity, and fragmentation of interactions among activation, cytotoxicity, and memory nodes, consistent with immune disorganization. Conversely, treated VL–HIV(T) patients exhibited increased connectivity and re-establishment of coordinated interactions between functional markers, indicating partial re-establishment of the MAIT cell immunological network architecture. Discussion Together, VL and VL–HIV co-infection are associated with quantitative depletion and qualitative dysregulation of circulating MAIT cells, characterized by concurrent hyperactivation and exhaustion, coupled with immunological network fragmentation, while liposomal amphotericin B treatment appears to promote partial immunological reorganization.