Pattern recognition receptor mediated downregulation of microRNA-650 fine-tunes MxA expression in dendritic cells infected with Influenza A virus

MicroRNAs (miRNAs) are important post-transcriptional 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 miRNA which is downregulated upon stimul...

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Bibliographic Details
Main Authors: Simmons, A, Pichulik, T, Khatamzas, E, Liu, X, Brain, O, Delmiro Garcia, M, Leslie, A, Danis, B, Mayer, A, Baban, D, Ragoussis, J, Weber, A
Format: Journal article
Language:English
Published: Wiley 2016
Description
Summary:MicroRNAs (miRNAs) are important post-transcriptional 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 miRNA which is downregulated upon stimulation of primary human monocyte-derived dendritic cells (MDDCs) with a variety of different microbe-associated molecular patterns (MAMPs). A comprehensive target search combining in silico analysis, transcriptional profiling and reporter assays reveals that miR-650 regulates several well-known interferon-stimulated genes (ISGs), 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.