T Cell Dysfunction in Cutaneous Leishmaniasis at Single-Cell Resolution
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Background
Cutaneous leishmaniasis (CL) is characterized by immune dysregulation that facilitates chronic infection.
Objective
To investigate the role of T cells in the immunopathology of CL by characterizing the immune landscape of skin lesions using single-cell RNA sequencing (scRNA-seq).
Methods
We performed scRNA-seq to profile T cells from PBMC and skin lesions of CL patients.
Results
We analyzed the transcriptional profile of distinct populations of CD4+ and CD8+ migratory T cells in CL lesions. CD8+ resident T cells displayed expression of exhaustion markers and were categorized into progenitor, transitional, and terminal stages, with HAVCR2 (TIM-3) identified as a potential driver of dysfunction. Compared to psoriasis and healthy skin, CL lesions showed a reduced frequency of regulatory T cells (Tregs), potentially linked to oxidative stress, DNA damage, and increased apoptosis. We also detected double-negative (DN) γδ T cells, suggesting their potential role in antigen presentation via MHC class II through TGF-β signaling.
Conclusion
This study provides novel insights into immune evasion mechanisms in CL, identifying TIM-3, Treg modulation, and the functional role of DN γδ T cells as distinct potential targets for future immunotherapies.
