Pattern Recognition Receptor Mediated Downregulation of microRNA-650 Fine-Tunes MxA Expression in Dendritic Cells Infected With Influenza A Virus

Eur J Immunol. 2016 Jan;46(1):167-77. doi: 10.1002/eji.201444970. Epub 2015 Oct 30.

Abstract

MicroRNAs are important posttranscriptional regulators of gene expression, which have been shown to fine-tune innate immune responses downstream of pattern recognition receptor (PRR) signaling. This study identifies miR-650 as a novel PRR-responsive microRNA that is downregulated upon stimulation of primary human monocyte-derived dendritic cells (MDDCs) with a variety of different microbe-associated molecular patterns. A comprehensive target search combining in silico analysis, transcriptional profiling, and reporter assays reveals that miR-650 regulates several well-known interferon-stimulated genes, including IFIT2 and MXA. In particular, downregulation of miR-650 in influenza A infected MDDCs enhances the expression of MxA and may therefore contribute to the establishment of an antiviral state. Together these findings reveal a novel link between miR-650 and the innate immune response in human MDDCs.

Keywords: Dendritic cells; Host/pathogens interactions; ISGs; Innate immunity; MicroRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Down-Regulation
  • Flow Cytometry
  • Gene Expression Regulation / genetics
  • Gene Expression Regulation / immunology*
  • Humans
  • Immunity, Innate / genetics*
  • Immunity, Innate / immunology
  • Immunoblotting
  • Influenza A virus / immunology*
  • MicroRNAs / genetics
  • MicroRNAs / immunology*
  • Microscopy, Confocal
  • Myxovirus Resistance Proteins / biosynthesis*
  • Myxovirus Resistance Proteins / immunology
  • Oligonucleotide Array Sequence Analysis
  • Receptors, Pattern Recognition / immunology
  • Signal Transduction
  • Transfection

Substances

  • MIRN650 microRNA, human
  • MX1 protein, human
  • MicroRNAs
  • Myxovirus Resistance Proteins
  • Receptors, Pattern Recognition