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Role of mirRNA21 and miRNA 148 on immune regulation of splenic leukocytes in canine visceral leishmaniasis


LVA Visceral leishmaniasis (LV) is a chronic and often fatal disease in man. According to the Secretary of Epidemiological Surveillance of the State of São Paulo, the disease is expanding with a high mortality rate, with the Araçatuba region concentrating a large number of cases in the state. Visceral Canine Leishmaniasis (LVC) is a serious public health problem because infected animals are powerful transmitters of the parasite to humans by the phlebotomain vector, and canine disease is more prevalent than the human disease and usually canine cases precede human cases. The dog is therefore an important target in the control measures. The progression of canine infection is accompanied by failure of cellular immunity with reduction of circulating lymphocytes and cytokines that suppress the function of macrophages. The function of the T cell in the induction of the cellular response is determinant for the elimination of the parasite inside the macrophages. Although immune suppression is already characterized, the determining factors are poorly understood. In the last decade studies have shown that the regulation of the effector function of macrophages and T cells seems to depend on miRNAs. There is much evidence of the role of miRNAs in regulating the expression of proteins that are critical for the development, function, and differentiation of various cellular types of the immune system. MiRNA 21 and miRNA 148a have increased expression in splenic leukocytes from dogs with VL and targets several proteins related to the immune response. Molecular tools will be used to increase or decrease miR21 and miR148a and the expression of the FAS, FASL, TNF-±, CD69, CCR7, IL-12 and TGF-beta,CD80 and iNOS proteins will be evaluated. Our results will improve our understanding of the pathogenesis of VL in the host, and as such, reveal new pathways that may be therapeutic targets. (AU)

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