Expressão de receptores inibitórios e seus ligantes em lesões de pacientes com leishmaniose cutânea localizada causada por Leishmania braziliensis

Abstract

Parasites from the Viannia subgenus that include Leishmania (Viannia) braziliensis are the most wide spread species in the Americas, causing cutaneous leishmaniasis (CL). The development of cutaneous lesions during CL is prevalent in more than 90% of cases and is characterized by an intense local cell-mediated TH1 immune response, production of cytolytic proteins and nitric oxide, which contribute to parasite control and tissue damage. In addition, increased production of pro-inflammatory mediators such as TNF-α and IFN-γ are observed systemically and locally in infected patients, playing an important role in the pathogenesis of the disease. This exacerbated inflammatory state can induce the expression of inhibitory receptors (IR), such as PD-1 and TIM-3, on the surface of T cells and their ligands on target cells, in which it’s effects during CL is poorly understood. Also, chronic inflammation can induce differentiation of memory T cells, which begin to express the surface markers such as KLRG1 and CD57, to an extend that their replicative rate is impaired, which could affect the disease’s control. In this scenario, we evaluated the expression of this molecules in local T cells, macrophages and neutrophils of patients with CL. Our results indicate that CL lesions have accumulated CD4+ and CD8+ cells and also express PD-1, TIM-3, KLRG1 and CD57 at a higher frequency than in normal skin. Furthermore, macrophages and neutrophils were found to be present at a higher frequency in patients than in healthy controls, being also the only group where PD-L1 and PD-L2 ligands were expressed. Our work contribute to a better understanting of IR and their role in the immunopathogenesis of CL, since their expression weaken the development of an immunologic response, which could impair the local response and contribute to parasite persistence.