Characterization of microRNA expression profiles in Leishmania-infected human phagocytes

Parasite Immunol. 2015 Jan;37(1):43-51. doi: 10.1111/pim.12156.

Abstract

Leishmania are intracellular protozoa that influence host immune responses eliciting parasite species-specific pathologies. MicroRNAs (miRNAs) 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 miRNAs associated with leishmanial infections. Normalized sequence read count profiles revealed a global downregulation in miRNA expression among host cells following infection. Most identified miRNAs 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 miRNAs 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 miRNAs upregulated in L. donovani-infected cells, these data provide evidence in support of a selective influence on host cell miRNA expression and regulation in response to differential Leishmania infections.

Keywords: Leishmania; Leishmaniasis; dendritic cell; macrophage; miRNA; microRNA.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cells, Cultured
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Dendritic Cells / parasitology*
  • Female
  • Gene Expression Regulation
  • Humans
  • Leishmania donovani / immunology
  • Leishmania donovani / physiology*
  • Leishmania major / immunology
  • Leishmania major / physiology*
  • Leishmaniasis / immunology
  • Leishmaniasis / parasitology
  • Leishmaniasis, Visceral / immunology
  • Leishmaniasis, Visceral / parasitology
  • MAP Kinase Signaling System / genetics
  • Macrophages / immunology
  • Macrophages / metabolism
  • Macrophages / parasitology*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Signal Transduction
  • Transforming Growth Factor beta / metabolism

Substances

  • MicroRNAs
  • Transforming Growth Factor beta