Circulating Soluble Factors and T-Cell Subsets as Immunological Predictors of Therapy Response in Human Cutaneous Leishmaniasis

Abstract

Background Human cutaneous leishmaniasis, a neglected tropical disease caused by Leishmania braziliensis, presents treatment challenges due to varying therapeutic responses. Current therapies often encounter limited efficacy and treatment failure, demanding a deeper understanding of immunopathogenesis and predictive markers. Methods We explored the immunological determinants influencing therapy response in human cutaneous leishmaniasis, focusing on the intricate host–parasite immune interactions. We evaluated blood and lesions from the same individuals before therapeutic intervention and followed the patients for 60 days to determine treatment efficacy. We employed multiparameter flow cytometry methods for peripheral blood analysis of soluble factors and T-cell subpopulations, and RNA sequencing for analysis of lesion biopsies. Results Our investigation identified a combined set of circulating soluble factors as promising noninvasive predictive markers for treatment outcomes. Additionally, we reveal an association between circulating CD8+ mucosal-associated invariant T (MAIT) cells with increased lesion pathology, and a gene signature in lesions associated with CD8+ MAIT cells in refractory patients. Conclusions These findings highlight the potential for tailored interventions and novel immunomodulatory strategies to enhance treatment efficacy and address challenges in unresponsive cases of this debilitating disease.