Analysis of miR-372 and miR-373 in metabolic shift on macrophages infected with Leishmania infantum.

Abstract

In this project, we aim to evaluate the function of miR-372/373 in the regulation of glucose metabolism in macrophages infected with Leishmania infantum. We hypothesize that the infection with L. infantum increases the expression of human miR-372/miR-373, and these molecules alter the mRNA/protein levels of HIF-1± and consequently a network of target genes involved in glycolysis in macrophages, increasing susceptibility to infection. Metabolomic approaches can clarify how metabolic intermediates are modulated during infection, and whether miR-372/373 family inhibition can block metabolic reprogramming. HIF-1± is a transcription factor related to the expression of genes that participate in glycolytic metabolism and the lactate production pathway. Leishmania can reprograms macrophage carbohydrate and lipid metabolism and induce inflammation. In previous data, we observed increased miR-372/373 in THP-1 macrophages infected with L. amazonensis and functional inhibition of these miRNA reduced infection. HIF1A 3'UTR mRNA is a predicted target of miR-372/373. Comparing the metabolic fingerprint of miR-372/373-inhibited to negative-control THP-1 macrophages would provide a big picture of the role of miR-372/373 in modulating macrophage metabolism during L. infantum infection, together with gene expression analysis and miRNA-target validation techniques.