Memory T Cell Subsets Expressing Tissue Homing Receptors and Chemokine Levels in Human Tegumentary Leishmaniasis

Abstract

Tegumentary leishmaniasis (TL) presents two main clinical forms: cutaneous (CL) and mucosal (ML) leishmaniasis affecting skin and nasopharyngeal mucosa. Due to parasite localization through disease stages, recruitment of T cells expressing chemokine receptors and their ligands will influence the generated host responses. The aim of this work was to characterize differential profiles of T cells expressing chemokine receptors and their plasma ligands by flow cytometry and ELISA. CL patients showed increased numbers of effector memory CD4+ T cells expressing skin homing receptors (CLA, CCR4), with the reversion of this effector phenotype observed after achieving clinical recovery. Meanwhile, ML patients showed higher frequencies of effector memory/terminal effector CD4+ and CD8+ T cells expressing chemokine receptors directed to skin (CLA, CCR4, CCR10) and mucosal (CCR6) tissues. Additionally, we reported that plasma amounts of ligands (CCL17, CCL20) vary according to the clinical form of TL. Finally, we demonstrated the ability of Leishmania spp. to modulate chemokine production (CCL17) in vitro. This work highlights the effector T cell response directed to skin and mucosal tissues in TL, emphasizing the role of cytotoxic functions in ML. The studied chemokine receptors could contribute to predicting disease progression and guiding future studies targeting relevant receptors to diminish pathogenic effector functions.