Fcγ‐RI, Fcγ‐RII and IL‐10 as predictive biomarkers for post‐therapeutic cicatrization time in monocytes from cutaneous leishmaniasis patients

Abstract

Cutaneous leishmaniasis (CL) treatment is based on therapy with Glucantime , yet, there are few laboratory methods to monitor its success. In this study, ex vivo and in vitro evaluations of peripheral blood monocytes were performed in a longitudinal study to characterize the impact of Glucantime on overall phenotypic/functional features of these cells from CL patients to identify predictive biomarkers for post-therapeutic monitoring by flow cytometry. The ex vivo evaluation from CL patients demonstrated a modulatory profile before treatment, with a decrease in TLR-2, FcγRII, HLA-DR, CD86, IFN-γR, TNF, IL-12, NO, and an increase in FcγRIII and IL-10R. Conversely, treatment changes some of these biomarker expressions by decreasing FcγRIII and IL-10R and increasing IFN-γR, IL-12 and NO. Moreover, an in vitro analysis of these patients showed a reduced phagocytic capacity of Leishmania braziliensis and higher levels of IL-10 and TGF-β modulating functional profile. Regardless of the compromised L. braziliensis phagocytic capacity, treatment re-established the production of IL-12, IL-10, TGF-β and NO at the basal level. Notably, monocytes from patients with early cicatrization showed enhanced FcγRI and FcγRII expressions and reduced IL-10, which was further corroborated by a baseline fold change analysis. Finally, the logistic regression model emphasized the performance of FcγRI, FcγRII and IL-10 as robust predictive biomarkers for post-therapeutic cicatrization during cutaneous leishmaniasis.

Leishmania infantum induces high phagocytic capacity and intracellular nitric oxide production by human proinflammatory monocyte

“…However, our group, in cutaneous leishmaniasis, showed protective immune response associate with CD23-IgE-mediated NO release, iNOS specific and increase of intracellular NO after treatment. (14,18) Thus, our data are in concordance with literature studies.…”

“…modulates monocytes/ macrophage functions by preventing oxidative burst and the effector functions that lead to its elimination and by improvement a bursting microenvironment of modulatory IL-4, IL-10, and TGF-β cytokines. (14,15,16,17,18) A better understanding of the immune response against Leishmania spp. is very important to establishing a rational approach to chemotherapy and to comprehend mechanism of drug resistance.…”