Alterações morfológicas e de populações celulares em baços de pacientes com formas graves de leishmaniose visceral humana

Abstract

INTRODUCTION: Visceral leishmaniasis (VL) is associated with splenic architectural changes and redistribution of cell populations involved in the immune response. AIM: The objectives of this dissertation were to study the spleen white pulp disruption in human visceral leishmaniasis (VL) and which cells and cytokines are involved in this process. METHODOLOGY: For this study, samples from 10 human spleens were analyzed, 7 obtained from splenectomies in patients with severe visceral leishmaniasis and 3 from splenectomies performed in individuals without leishmaniasis. Six of the VL patients are co-infected with the human immunodeficiency virus (HIV), with an undetectable viral load. In this study, we aimed to evaluate whether changes observed in spleens in murine and canine models are also present in the human spleen during the course of visceral leishmaniasis, considering that there are still few studies on the subject in humans. Spleen sections were labeled with anti-CD3, CD4, CD8, CD20, CD79-α, CD68, Caspase 3, FoxP3, IFNg, IL-1b, IL-4, IL-6, IL-10, IL-17, TGFβ and TNFα antibodies. RESULTS: The observed results of the comparison between LV and spleen without LV showed red cell plasmacytosis, hyperplasia or atrophy and disruption of the white pulp, as well as a reduction in the CD4 + T cell population, an increase in the CD8 + T lymphocyte population and a reduction in CD20 + cells in the red pulp. Among the cytokines, there was reduction of IL-10, IL-17 in white pulp and red pulp. And, in white pulp, there was increased expression of TNF, Foxp3 and Caspase3 in spleens with visceral leishmaniasis. CONCLUSIONS: These findings are compatible with an inefficient immune response to antigenic overexposure to LV-HIV co-infection, culminating in exhaustion, when cells lose efficient immune response capacity, with less or no production of protective molecules for the host and production of inhibitory molecules, which favors the aggravation of the disease. It is worth mentioning that chronic antigenic hyperstimulation leads to persistent activation, which causes exhaustion of the immune system.