METALOPROTEINASES MATRIX EVALUATION IN DOGS NATURALLY INFECTED WITH Leishmania infantum
Canine Visceral Leishmaniasis. Metalloproteinases (MMPs). Immunopathogenesis. Leishmania infantum.
Dogs are the primary reservoir of Leishmania parasites. The immune response induced by Leishmania infantum is important for resistance to infection and pathogenesis in these animals. Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes that play multiple roles in immune response and matrix remodeling. However, the action of these enzymes may lead to immunopathology in an infectious process that causes host morbidity or mortality and favors the spread of the pathogen and its persistence. Few studies demonstrate the correlation between MMPs expression and clinical manifestations of animals with canine visceral leishmaniasis (CVL). Thus, the objective of this study was to evaluate the expression of matrix metalloproteinases in dogs naturally infected with Leishmania infantum and correlate them to the clinical manifestations of the disease (asymptomatic, oligosymptomatic, symptomatic). For this, the relative expression of MMPs, their tissue inhibitors (TIMPs) and the cytokines, IL-10 and TNF-α, was analyzed in the liver tissue of dogs by real time PCR. The inflammatory process and cytostructure of the liver tissue were measured using hematoxylin-eosin staining. Only symptomatic and oligosymptomatic dogs showed greater expression of MMP-2, when compared to the group of asymptomatic dogs. In addition, oligosymptomatic dogs showed a larger and more diffuse hepatic inflammatory infiltrate when compared to asymptomatic and symptomatic dogs. On the other hand, all dogs infected with L. infantum showed higher expression of tissue inhibitors TIMP-1 and TIMP-4 when compared to uninfected animals. Further more, symptomatic dogs showed a greater expression of the cytokine IL-10 when compared to the other groups. The results demonstrate high expression of MMPs (MMP2, MMP3, MMP9, MMP11 and MMP13) and TIMPs (TIMP1 and TIMP4) is positively correlated with a higher expression of the cytokines TNF-α and IL10 in dogs naturally infected by L. infantum, contributing to destruction of the liver parenchyma and for the clinical evolution of visceral leishmaniasis in animals.