miRNA expression in human macrophage-like cells infected by Leishmania infantum and their interaction with mRNAs

MicroRNAs (miRNAs) regulate gene expression and play a crucial role in numerous diseases, including infections. Leishmaniasis is a neglected infectious disease occurring in different forms (i.e., cutaneous, mucocutaneous, and visceral) caused by protozoans belonging to the Leishmania genus. The parasite infects mainly the macrophages, establishing a niche permissive for its proliferation. Although Leishmania parasites are known to modulate host gene expression, the role of host miRNAs in this process has not been fully characterized. This work aimed to study miRNA expression profile in human macrophage-like cells infected by L. infantum, the causative agent of visceral and cutaneous leishmaniasis in the Mediterranean region. Moreover, we attempted to identify putative miRNA-mRNA interactions based on the mRNA expression changes previously described1. To this end, small RNA-seq was performed in U937 cells infected with L. infantum after 24 h and 48 h, and differentially expressed miRNAs were identified and validated through qPCR. The upregulated and downregulated miRNAs at 24h (n=24, 29) and 48h (n=31, 15) were subjected to functional enrichment analysis. Some enriched ontologies were related to pathways identified in previous work based on mRNA-seq on the same samples, providing the basis for identifying miRNAmRNA interactions. To this end, miRNAs putative targets were defined using Targetscan 8.0; then, the target lists were compared with dysregulated genes identified in the same experimental conditions, and miRNA-mRNA networks were predicted. Interestingly, the miRNAs commonly dysregulated at both 24h and 48h post-infection targeted several dysregulated transcription factors (TFs), evidencing a relationship among miRNAs and TFs that can contribute to Leishmania-induced immune subversion into macrophages.