LXPLEEN: estudo dos genes e células envolvidas com a desorganização esplênica na leishmaniose visceral recidivante

Abstract

BACKGROUND: Visceral leishmaniasis (VL) is a neglected zoonosis that has considerable impacts on public health. One of the problems related to VL is the emergence of severe forms that lead to the death of 6-8% of patients, even during treatment. In addition, some patients develop a recurrent form, with the occurrence of multiple returns to the hospital in a brief period. The spleen is a lymphoid organ responsible for hemocateresis and immunological surveillance and it engages in pathogenesis of VL, presenting disorganization of the white pulp (WP) and extensive replacements of the normal cellularity of the red pulp (RP) by plasma cells. Despite this, little is known about the contribution of splenic disruption in human VL and how changes in splenic cellularity change the profile of cytokine production in the organ, favoring susceptibility to infection. AIM: Our objective is to define which cells and signaling pathways participate in the disruption of splenic compartments and what is the association with progression in relapsed VL. MATERIAL AND METHODS: Using spleens from 6 patients with relapsed VL and 5 control patients, we performed immunohistochemistry to evaluate the distribution and relationship of leukocytes (T and Treg lymphocytes, B lymphocytes, macrophages and plasma cells) and cytokines (IL1B, IL4, IL6, IL10, IL17, IFNγ, TNF and TGF) in the WP and RP of the spleen. Furthermore, were performed the gene expression analysis and identification of DEG profiles and gene interaction networks involved with relapsing VL. RESULTS: There is an accumulation of macrophages and plasma cells in the RP of patients with VL, with reduced apoptosis and expression of genes related to lymphocyte migration; There is increased expression of BCL10 and ICOSLG; The IL6 signaling pathway is overexpressed in VL patients, and there is an increase in the amount of total IL6 and a negative correlation between IL6 and splenic WP percentage; There is negative correlation between the number of circulating leukocytes and the number of splenic leukocytes. CONCLUSIONS: In patients with recurrent VL, there is an accumulation of cells in the spleen mediated by reduced apoptosis and cell migration, corroborating to hypersplenism. Furthermore, the IL6 signaling pathway contributes to spleen disorganization.