title: Pattern recognition receptor mediated downregulation of microRNA-650 fine-tunes MxA expression in dendritic cells infected with influenza A virus.
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.
authors.affiliation: MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, UK.|Department of Immunology, Interfaculty Institute for Cell Biology, University of Tübingen, Tübingen, Germany.
authors.forename: Tica
authors.initials: T
authors.lastname: Pichulik
authors.affiliation: MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, UK.
authors.forename: Elham
authors.initials: E
authors.lastname: Khatamzas
authors.affiliation: Department of Immunology, Interfaculty Institute for Cell Biology, University of Tübingen, Tübingen, Germany.
authors.forename: Xiao
authors.initials: X
authors.lastname: Liu
authors.affiliation: MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, UK.|Translational Gastroenterology Unit, John Radcliffe Hospital, Headington, Oxford, UK.
authors.forename: Oliver
authors.initials: O
authors.lastname: Brain
authors.affiliation: Department of Immunology, Interfaculty Institute for Cell Biology, University of Tübingen, Tübingen, Germany.
authors.forename: Magno
authors.initials: M
authors.lastname: Delmiro Garcia
authors.affiliation: MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, UK.
authors.forename: Alasdair
authors.initials: A
authors.lastname: Leslie
authors.affiliation: MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, UK.
authors.forename: Benedicte
authors.initials: B
authors.lastname: Danis
authors.affiliation: MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, UK.
authors.forename: Alice
authors.initials: A
authors.lastname: Mayer
authors.affiliation: Wellcome Trust Centre for Human Genetics, Oxford, UK.
authors.forename: Dilair
authors.initials: D
authors.lastname: Baban
authors.affiliation: Wellcome Trust Centre for Human Genetics, Oxford, UK.
authors.forename: Jiannis
authors.initials: J
authors.lastname: Ragoussis
authors.affiliation: Department of Immunology, Interfaculty Institute for Cell Biology, University of Tübingen, Tübingen, Germany.
authors.forename: Alexander N R
authors.initials: AN
authors.lastname: Weber
authors.affiliation: MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, UK.|Translational Gastroenterology Unit, John Radcliffe Hospital, Headington, Oxford, UK.
authors.forename: Alison
authors.initials: A
authors.lastname: Simmons
mesh_terms: D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D015536:Down-Regulation; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics* / Q000276:immunology; D015151:Immunoblotting; D009980:Influenza A virus / Q000276:immunology*; D035683:MicroRNAs / Q000235:genetics / Q000276:immunology*; D018613:Microscopy, Confocal; D064547:Myxovirus Resistance Proteins / Q000096:biosynthesis* / Q000276:immunology; D020411:Oligonucleotide Array Sequence Analysis; D051192:Receptors, Pattern Recognition / Q000276:immunology; D015398:Signal Transduction; D014162:Transfection
chemical_list: C550124:MIRN650 microRNA, human; C579071:MX1 protein, human; D035683:MicroRNAs; D064547:Myxovirus Resistance Proteins; D051192:Receptors, Pattern Recognition
keywords: Dendritic cells; Host/pathogens interactions; ISGs; Innate immunity; MicroRNA