THE ROLE OF CHEMOKINES WITH SKIN AND NASAL MUCOSAL TROPISM IN THE OUTCOME OF AMERICAN TEGUMENTARY LEISHMANIASIS (ATL)

PIMENTEL J, GARCÍA BUSTOS MF, MARCO JD, BARROSO P, RAGONE P, MESÍAS A, PÉREZ BRANDÁN C, ACUÑA L, PARODI C.

Congreso; SAIB - SAMIGE Joint meeting; 2021

The purpose of this work was to study the involvement of the chemokines CCL20 and CCL17 commanded to skin and mucosal tissues in ATL. Chemokines such as CCL20 and CCL17 are cytokines with chemoattractant properties that are related to the leukocyte trafficking towards injury tissues during inflammation processes. There are two different clinical manifestations of ATL: cutaneous leishmanias (CL) characterized by delimitated skin ulcers and mucocutaneous leishmaniasis (ML) which is the most severe form of the disease with compromise of mucosal and pharyngeal tissues. Peripheral blood samples were extracted from a total of 35 patients: 20 patients with CL, 15 with ML and 10 healthy subjects. We measured plasma levels of chemokines by ELISA. By flow cytometry analysis we evaluated the chemokine receptors CCR4 and CCR6 on CD45RO+ CD4+ and CD8+ T cells. Also, isolated PMBCs were cultured (1x106 cells/ml, 7 days, 5% CO2) in presence of L. braziliensis or L. amazonensis soluble antigens (20ug/ml) during in vitro studies. In order to investigate gen variations of CCL20, CCL17 and their receptor CCR4, single nucleotide polymorphisms (SNP) assays by RLP-PCR and gene fragment digestion were performed. We found higher plasma levels of CCL20 (p=0.0017) and lower concentrations of CCL17 (p=0.0023) in patients with ML. The production of CCL17 in in vitro assays was suppressed (p=0.0085) by the presence of L. amazonensis antigens in ML patients while L. braziliensis proteins seems to slightly improve CCL20 production in both ML and CL patients. We suggest that the presence of Leishmania spp. could influence the chemokine responses and that different clinical forms of the disease might present altered chemokine patterns. Similar percentages of CD4 and CD8 T cells expressing CCR4+ and CCR6+ receptors were observed among groups with the majority of them within the CD45RO+ population, indicating that for CL and ML distinct memory subsets harbor the required receptors to respond to their ligands. For SNP analysis we found higher CT genotype frequencies for CCL17 (CL, 72%; ML, 44%; HS, 80%), while TT genotype predominated for CCL20 (CL, 45%; ML, 87%; HS, 60%). We will perform further studies in order to confirm if higher frequencies of a determined genotype are related with distinct clinical outcomes