MicroRNAs involved in post-transcriptional regulation of modulated genes in patients with Tegumentary Leishmaniasis caused by Leishmania (Viannia) guyanensis

Abstract

Leishmaniasis are diseases caused by protozoa of the Leishmania genus and manifest as cutaneous, mucosal or visceral disease. In Brazil, Tegumentary Leishmaniasis (TL) is mainly caused by 3 species: Leishmania (Viannia) braziliensis, L. (Leishmania) amazonenses and L. (V.) guyanensis. The TL caused by L. (V.) guyanensis presents mainly in the cutaneous form and its occurrence is concentrated mainly in the Amazon region of the country. Regarding the pathogenesis of TL, studies show that the potent inflammatory response developed by the host, important to control the infection, can lead to tissue damage and development of characteristic lesions, and this fact may be associated with several factors not specific to the parasite, among them , the epigenetics. In TL caused by L. (V.) braziliensis, alterations in the expression of microRNAs in the experimentally infected cell and in patient plasma have been described and related to parasite proliferation and inflammatory process. Considering that different species of Leishmania have peculiarities in their interaction with the host, with reflection on the evolution of infection and disease, the study of gene control at different levels induced by L. (V.) guyanensis is of paramount importance to unravel its pathogenic mechanisms. Thus, this project will explore the molecular mechanisms in the pathogenesis of L. (V.) guyanensis, focusing on the expression of microRNAs related to the inflammatory process in plasma of patients with tegumentary leishmaniasis, before and after treatment, and in cells of the monocytic lineage human THP-1 infected with L. (V.) guyanensis. MicroRNA with significantly altered expression in patient plasma and in vitro infection will be validated, aiming at elucidating its participation in the pathogenesis and, at the same time, its evaluation as prognostic biomarkers and/or target for therapeutic intervention.