IL-32-producing CD8+ memory T cells define immunoregulatory niches in human cutaneous leishmaniasis

Area of Science:

• Immunology
• Dermatology
• Parasitology

Background:

• Human cutaneous leishmaniasis (CL) presents chronic skin pathology.
• Immune checkpoints (ICs) are implicated in CL disease progression, but their specific cellular and molecular niches remain unclear.
• Previous studies indicated indoleamine 2,3-dioxygenase 1 (IDO1) and programmed death-ligand 1 (PD-L1) enrichment in CL lesions.

Purpose of the Study:

• To define the cellular and molecular niches of immune checkpoint expression in cutaneous leishmaniasis.
• To investigate the role of IL-32-expressing cells in the IDO1/PD-L1 niche.
• To identify potential biomarkers for treatment response in CL.

Main Methods:

• Spatial cell interaction mapping was employed to analyze skin lesions from patients with CL.
• Immunohistochemistry and cell-specific staining were used to identify cell types and marker expression.
• Correlation analysis was performed to link cell abundance with treatment outcomes.

Main Results:

• IDO1 and PD-L1 were found to be enriched in skin lesions of Sri Lankan CL patients.
• IL-32-expressing CD8+ memory T cells and regulatory T cells (Tregs) were identified as key components of the IDO1/PD-L1 niche across different CL patient cohorts (Sri Lanka, Brazil, India).
• Higher abundance of IL-32+ cells and IL-32+CD8+ T cells at treatment initiation correlated negatively with cure rates in Sri Lankan patients.

Conclusions:

• This study elucidates the spatial mechanisms of immune checkpoint expression in CL, highlighting the role of IL-32+ T cells and Tregs.
• The findings suggest that IL-32+ cell counts at treatment initiation could serve as a predictive biomarker for antimonial therapy response in CL.
• Identifying these cellular niches provides a strategy for discovering novel biomarkers and understanding treatment resistance in leishmaniasis.