Avaliação do perfil fenotípico-funcional de monócitos de pacientes portadores de leishmaniose cutânea localizada, tratados com o antimoniato de N-metil glucamina

Abstract

Infections caused by Leishmania braziliensis present diverse clinical manifestations and, localized cutaneous leishmaniasis (LCL) is the most common. Although there are several studies that evaluate specific aspects of the cellular immune response in human LCL, there are few published studies evaluating the immunological events associated with the Leishmania/ phagocytes interaction. In this study, the primary objective was to evaluate the rate of internalization of L. braziliensis promastigotes and characterize the phenotypic and functional aspects, by evaluating the cellular surface markers expression profile (TLR-2, TLR-4, CD16, CD32, CD64, IL-10R, IFN-R, HLA-DR, CD80 e CD86), cytokine profile (TNF-, IL-12, IL-10 e TGF-) and the levels of intracellular nitric oxide in peripheral blood monocytes, in the absence and presence of L. braziliensis promastigotes. To achieve the goals, healthy volunteers (CS, N = 10) and LCL patients attended at the Leishmaniasis Reference Center of René Rachou Research Center at the time of the first evaluation before treatment (T0 LC, N = 10) and 90 days after treatment (T90 LC, N = 10), were evaluated. Hence, this wide and prospective study that involves analysis of phenotypic and functional aspects of monocytes, target cell for Leishmania, is a unique approach that may contribute to better understanding of the host-parasite relation in the context of LT. The achieved results demonstrate that monocytes from patients evaluated before treatment, showed low production of TNF-α and NO associated with a low expression of TLR2, CD32, HLA-DR and CD86, and high production of IL-10, TGF-β and IL-10R. After treatment, monocytes showed a high production of TNF-α, IL-12 and NO associated with an increased expression of IFN-γ, TLR4, CD64 and CD86, and low production of IL-10, TGF-β and IL-10R. Thereby, in active disease, the modulated immune response is important for the establishment of infection and for the control of the inflammatory response that establishes with the evolution of the disease, which is critical to indicate the degree of disease severity. After treatment and clinical cure, became evident the role of the inflammatory response which, besides is indicative of the good response to treatment, is essential to prevent reactivation of the lesions, thus stimulating the ability of monocyte/macrophages to control the infection in case of a new contact with the parasite.