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

In this study, we described, for the first time, specific aspects of an anti-Leishmania immune response in a Brazilian Xakriaba indigenous community. Induction of an intracellular NO pathway, triggered by the binding of IgE to CD23 receptor in IFN-/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 (LCL60). 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 LCL60). We also showed that the increased frequency of IFN-(+) 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-(+)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-(+)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 LCL60 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.