Characterization of Regulatory T Cells in Patients Infected by Leishmania Infantum

Abstract

High IL-10 levels are pivotal to parasite survival in visceral leishmaniasis (VL). Antigenic stimuli induce IL-10 expression and release of adenosine by CD39/CD73. Due their intrinsic ability to express IL-10 and produce adenosine from extracellular ATP, we evaluated the IL-10, CD39, and CD73 expression by Regulatory T cells (Treg) correlated with VL pathology. Using flow cytometry, Treg cells was analyzed in peripheral blood samples from VL patients (in the presence and absence of Leishmania infantum soluble antigen (SLA)) and healthy individuals (negative endemic control—NEC group), without any treatment. Additionally, IL-10 levels in leukocytes culture supernatant were measured in all groups by ELISA assay. VL patients presented more Treg frequency than NEC group, independently of stimulation. ELISA results demonstrated that SLA induced higher IL-10 expression in the VL group. However, the NEC group had a higher Treg IL-10+ compared to the VL group without stimulation and SLA restored the IL-10 in Treg. Additionally, an increase in Treg CD73+ in the VL group independently of stimuli compared to that in the NEC group was observed. We suggest that Treg are not the main source of IL-10, while the CD73 pathway may be an attempt to modulate the exacerbation of immune response in VL disease.

Memory T cells: promising biomarkers for evaluating protection and vaccine efficacy against leishmaniasis

“…In a model of VL infection, it has been suggested that transition of the inflammatory milieu to a regulatory milieu, shown by the increased B-cell activity and IL-10 levels, is associated with the establishment of chronic infection and accumulation of Leishmania parasites in the skin ( 104 ). In human leishmaniasis, IL-10 plays a central role in the course of the immune response in VL, contributing to the chronicity of the disease through suppression of host immunity and effector T-cell functions ( 59 , 106 , 107 ). Indeed, it was shown that elevated levels of plasma IL-10 and IL-10 expression by keratinocytes indicate the likelihood of subsequent PKDL development in VL patients following treatment ( 108 ).…”