MicroRNA profile of human macrophages derived from the THP-1 cell line infected with Leishmania (L.) amazonensis

Abstract

The establishment of Leishmania infection in macrophages depends on the subversion of the immune response of this host cell to the parasite. One of these subversion mechanisms consists in the modulation of the L-arginine metabolism, a common substrate of nitric oxide (NO) and polyamines production pathways. This regulation directly influences the survival of the amastigote in the phagolysosome, since NO production is decreased in detriment of a higher production of polyamines, essential for Leishmania replication. It is known that this is possible, since the parasite is capable of increasing the expression of arginase 1 in the host macrophage, although the molecular mechanisms involved in this process has not been described yet. The project is based on the hypothesis that this subversion can be regulated by post-transcriptional mechanisms by modifying the profile of microRNAs (miRNA) of the macrophages exposed to L. (L.) amazonensis infection, evaluated in this project in wildtype or arginase knockout parasites. Preliminary results from the laboratory indicated that this regulation occured in murine macrophages. The aim of the project is to evaluate if the alteration of miRNA profile also occurs in human macrophages derived from the THP-1 monocytic line, making possible a later comparison of these results. Confirming the alteration of the miRNA expression in these cells, the study will extend to the identification of the target mRNAs involved in the pathways of interest (polyamines/NO) and the control of arginase and/or NOS2 enzymes is expected. (AU)