Evaluation of the role of microRNAs in American tegumentary leishmaniasis.

Abstract

Although the pathogenesis of American tegumentary leishmaniasis (ATL) caused by L (V.) braziliensis is not fully understood, it is known that the emergence of the lesion and its later resolution or aggravation are related to the immune response of the individual. Thus, patients with the cutaneous localized form, which tend to heal spontaneously, present a response capable of eliminating the parasite without excessive tissue damage. On the other hand individuals with the mucosal outcome of leishmaniasis present an exacerbated inflammatory response, suggesting that the aggravation of the inflammatory process in the lesion is due to failures in regulating the immune response against L. (V.) braziliensis. Such failures may be related to altered microRNAs expression, and previous works demonstrated that Leishmania may deregulate in its favor the expression of these molecules. Therefore, it becomes relevant to verify whether the lesion formation and aggravation in patients with ATL are supported by a post-transcriptional blockade caused by the altered MiRNAs expression that regulate the inflammatory response. Furthermore, it is interesting to investigate if spontaneous healing, as well as the lesion development in the active disease, is influenced or not by miRNAs expression, which are also found in the extracellular milieu. Alterations in the expression profile of these molecules in plasma samples were previously associated to various diseases. Considering these aspects, this project intends initially to characterize the miRNAs in sera of patients with active lesion and in others with clinical spontaneous healing. The possible presence of distinct miRNAs in the evaluated groups will point the potential of these molecules to serve as biological markers of the prognosis of ATL. The next step will consist in infecting human monocyte cell line THP-1 with L. (V.) braziliensis promastigotes and, after that, the levels of miRNAs expressed by these cells will be evaluated using qPCR. With this approach, it is intended to confirm that the parasite is able to cause changes in the expression of miRNAs in these cells. Next, the description of the targets of miRNAs expressed during infection in vitro by L. (V.) braziliensis will be performed using the DIANA miRPath 2.0 software tool. The set of results obtained in this project will generate knowledge base and subsidies for the development of new treatment alternatives against ATL.