Concentração sorológica da metaloproteinase da Matriz 2 em cães naturalmente infectados por Leishmania sp

Abstract

Visceral leishmaniasis (VL) is a disease caused by the protozoan Leishmania; it has a zoonotic character where the domestic dog is considered the main urban reservoir in the disease transmission cycle. In these animals, VL is characterized as a chronic systemic disease, and can classify them as symptomatic animals (when presenting clinical signs) or asymptomatic animals (with no clinical signs). Leishmania infection activates macrophages resulting in the release of several leishmanicide agents. Matrix metalloproteinases (MMP) are enzymes secreted by inflammatory and stromal processes of cells in response to exogenous insults and modulate the gradients of chemokines and cytokines that degrade the extracellular matrix which, in excess, can cause severe tissue damage. In animals, studies have shown an increase in these enzymes in conditions such as brain neoplasms, chronic enteropathies and VL in dogs. Since MMP-2 is considered as a flag of inflammation, the aim of this study is to evaluate the serum concentration of MMP-2 in dogs naturally infected with Leishmania sp. We used serum samples (n=166) previously collected from dogs of different sex breeds, aged over 6 months from the municipalities of Aracaju and Nossa Senhora da Glória, Sergipe. Serum samples were divided into three experimental groups based on diagnosis based on the Immunochromatographic DPP screening test® and the confirmatory serological test of leishmaniasis by immunoenzymatic assay (ELISA) and in the presence of clinical signs of visceral leishmaniasis: symptomatic group, asymptomatic group and control group composed of healthy uninfected dogs. The total MMP-2 concentration was determined using ELISA from 80 samples subdivided into case group n = 55 and control group n = 25. Descriptive and statistical analysis of the data was performed, the Kolmogorov-Smirnov normality test was applied, which were expressed with median and interquartile interval. The Kruskal-Wallis Test was used, a non-parametric test for the comparison between groups: seroreagent and non reagent and asymptomatic, symptomatic and control. Fisher's exact test was used to verify the correlation between clinical signs and characteristics of seroreagent dogs and serum concentrations d to MMP-2. A p < 0.05 was considered statistically significant. All statistical analyses were performed in the GraphPad Prism 9.0 software. All dogs expressed serum levels of MMP-2, however the seroreagent dogs expressed a significant increase in serum levels when compared to the control group. There was no statistically significant difference in relation to MMP-2 concentrations between symptomatic and asymptomatic seroreagent groups and in animals with different clinical manifestations. Several studies suggest that MMP-2 is released in the first phase of infection with a balanced production of Th1 and Th2 cytokines. Therefore, studies involving MMPs in canine visceral leishmaniasis can serve as a basis for a better understanding of the mechanisms of persistence and dissemination of Leishmania and serve as a possible diagnostic biomarker beyond staging and follow-up of the evolution in the treatment of the disease.