Protective Profile Involving CD23/IgE-mediated NO Release is a Hallmark of Cutaneous Leishmaniasis Patients from the Xakriabá Indigenous Community in Minas Gerais, Brazil

Abstract

In this study, we described, for the first time, specific aspects of an anti-Leishmania immune response in a Brazilian Xakriabá indigenous community. Induction of an intracellular NO pathway, triggered by the binding of IgE to CD23 receptor in IFN-γ/IL-4 cytokines environment, was evaluated in localized cutaneous leishmaniasis (LCL) carriers and positive Montenegro skin test (MST) individuals without skin lesion (MT+SL-). Our data demonstrated that the higher frequency of CD23+CD14+ monocytes and the increased serum levels of IgE observed in the LCL group were even higher in LCL carriers with late lesions (LCL≥60). Furthermore, patients with LCL presented increased NO production after Leishmania (Viannia) braziliensis stimulation and this NO profile was independent of the time of the lesion (recent LCL<60 or late LCL≥60). We also showed that the increased frequency of IFN-γ+ and IL-4+CD4+ T cells is related to the MT+SL- group. The results of biomarker signature curves demonstrated that in the MT+SL- group, the index signature was characterized by DAF-2T+CD14+/IL-4+CD8+/IFN-γ+CD4+/IL-4+CD4+. On the other hand, the LCL group presented a higher index of DAF-2T+CD14+/CD23+CD14+/IL-4+ CD8+, associated with a lower index of IFN-γ+CD8+. Considering the time of lesion, data analysis demonstrated that the main differences observed were highlighted in LCL<60 patients, with a higher index of CD23+CD14+, which was also present in LCL≥60 patients. In conclusion, our data suggest that the protective immune response involving CD23-IgE-mediated NO release is a hallmark of patients with LCL. However, in MT+SL- individuals, another different leishmanicidal mechanism seems to be involved.