Correlação entre a resposta imunológica e as manifestações clínicas na Leishmaniose Visceral Canina

Abstract

Dogs are the primary reservoirs of the parasites of the genus Leishmania. The immune response induced by infection with Leishmania infantum in these animals is not completely understood, and few studies have investigated the correlation between the expression of cytokines and chemokines and clinical manifestations of animals with canine visceral leishmaniasis (CVL). The aim of this study was to correlate the clinical status of dogs naturally infected with L. infantum (rural municipality of Mossoro, Rio Grande do Norte, Brazil) with the expression levels of cytokines (IFN-γ, TNF-α, IL-10 and IL-17), iNOS, chemokines (CCL1, CCL2, CCL3, CCL4, CCL5, CCL17, CCL20, CCL24, CCL26, CXCL9, CXCL10), chemokine receptors (CXCR3, CCR3, CCR4, CCR5, CCR6, CCR8), and parasitism in the liver and spleen using real-time PCR. Initially, we conducted seroepidemiological survey of dogs from 12 rural settlements from Mossoró-RN, totaling 398 dogs examined. The positivity of dogs for the parasite was determined by reativity in two serological tests (ELISA and IFA). All rural localities showed dogs positive for L. infantum, with positivity varying between 6,6% and 49% of the animals examined by location, totalizing 27% of dogs from all settlements. Subsequently, Twenty-one dogs were clinically evaluated and classified as asymptomatic (n = 11) or symptomatic (n = 10). The infection was confirmed by performing imprint in the spleen, and observation of amastigotes. Splenomegaly, weight loss and onychogryphosis were the most frequent clinical signs. In the liver, levels of mRNA expression of cytokines (IFN-γ, TNF-α, IL-10 and IL-17), iNOS and chemokines (CCL1, CCL17, CCL26, CCR3, CCR4, CCR5, CCR6, CCR8 and) were lower in symptomatic animals than in asymptomatic animals. In comparison with uninfected animals, symptomatic dogs had lower levels of expression of almost all molecules tested. In addition, the parasitic load was observed high and low symptomatic hepatic inflammation in animals when compared to asymptomatic. In conclusion, the decreased expression of cytokines, chemokines and chemokine receptors result in poor migration and activation of leukocytes, hindering control of parasitism and leading to the development of the disease.