Host-parasite interactions after in vitro infection of human macrophages by Leishmania major: Dual analysis of microRNA and mRNA profiles reveals regulation of key processes through time kinetics.

Abstract

Micro-RNAs are a class of small non-coding ribonucleic acids that concomitantly regulate the expression of tens to hundreds of genes. To reduce the host's defense, Leishmania parasites hijack the cellular functions of their macrophage's targets through gene expression regulation. Only few studies have attempted to correlate miRNAs and mRNAs expressions within the same samples in the context of cellular parasitism. In this study, the profiling of human macrophages, in vitro infected by L. major parasites, was performed at both the mRNA transcriptomic level and the expression of a set of 365 miRNAs, and we correlated their expressions in search for a common molecular signature. Both mRNA and miRNA profiles were monitored during the first 24 h post-infection to capture potential time-dependent fluctuations. We then cross-correlated the cellular biological processes and the pathways associated to the predicted targets of miRNAs and to the differentially expressed mRNAs at all time points of infection on the same samples. Besides revealing the classical activation of immune signaling pathways, the mRNA-micro-RNAs correlation study highlighted other common regulatory inflammatory biological processes, allowing identification of rapidly modulated pathways, and bringing further evidence on the early molecular cross talk that take place between Leishmania and infected cells.