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 and their tissue inhibitors (TIMPs) 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. All dogs infected with Leishmania infantum showed high expression of MMPs when compared to uninfected dogs. However, only symptomatic and oligosyntomatic dogs showed higher MMP-2 e -11 expression when compared to the asyntomatic dogs. Moreover, oligosymptomatic dogs had a larger and more diffuse hepatic inflammatory infiltrate when compared to asymptomatic and symptomatic dogs. On the other hand, all dogs infected by L. infantum showed higher expression of TIMP-1 tissue inhibitor when compared to uninfected animals. The results demonstrate high expression of MMPs (MMP2, MMP3, MMP9, MMP11 and MMP13) in dogs naturally infected by L. infantum and greater inflammatory infiltrate in the liver of oligosymptomatic dogs, which may contribute to the destruction of the liver parenchyma and the clinical evolution of visceral leishmaniasis in animals.