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Leishmania are intracellular protozoa that influence host immune responses eliciting parasite species-specific pathologies. Micro RNAs (mi RNAs) are short single-stranded ribonucleic acids that complement gene transcripts to block protein translation and have been shown to regulate immune system molecular mechanisms. Human monocyte-derived dendritic cells ( DC) and macrophages ( MP) were infected in vitro with Leishmania major or Leishmania donovani parasites. Small RNAs were isolated from total RNA and sequenced to identify mature mi RNAs associated with leishmanial infections. Normalized sequence read count profiles revealed a global downregulation in mi RNA expression among host cells following infection. Most identified mi RNAs were expressed at higher levels in L. donovani-infected cells relative to L. major-infected cells. Pathway enrichments using in silico-predicted gene targets of differentially expressed mi RNAs showed evidence of potentially universal MAP kinase signalling pathway effects. Whereas JAK- STAT and TGF-β signalling pathways were more highly enriched using targets of mi RNAs upregulated in L. donovani-infected cells, these data provide evidence in support of a selective influence on host cell mi RNA expression and regulation in response to differential Leishmania infections. [ABSTRACT FROM AUTHOR]