title: Specific and Novel microRNAs Are Regulated as Response to Fungal Infection in Human Dendritic Cells.
abstract: Within the last two decades, the incidence of invasive fungal infections has been significantly increased. They are characterized by high mortality rates and are often caused byCandida albicansandAspergillus fumigatus. The increasing number of infections underlines the necessity for additional anti-fungal therapies, which require extended knowledge of gene regulations during fungal infection. MicroRNAs are regulators of important cellular processes, including the immune response. By analyzing their regulation and impact on target genes, novel therapeutic and diagnostic approaches may be developed. Here, we examine the role of microRNAs in human dendritic cells during fungal infection. Dendritic cells represent the bridge between the innate and the adaptive immune systems. Therefore, analysis of gene regulation of dendritic cells is of particular significance. By applying next-generation sequencing of small RNAs, we quantify microRNA expression in monocyte-derived dendritic cells after 6 and 12 h of infection withC. albicansandA. fumigatusas well as treatment with lipopolysaccharides (LPS). We identified 26 microRNAs that are differentially regulated after infection by the fungi or LPS. Three and five of them are specific for fungal infections after 6 and 12 h, respectively. We further validated interactions of miR-132-5p and miR-212-5p with immunological relevant target genes, such asFKBP1B, KLF4, andSPN, on both RNA and protein level. Our results indicate that these microRNAs fine-tune the expression of immune-related target genes during fungal infection. Beyond that, we identified previously undiscovered microRNAs. We validated three novel microRNAs via qRT-PCR. A comparison with known microRNAs revealed possible relations with the miR-378 family and miR-1260a/b for two of them, while the third one features a unique sequence with no resemblance to known microRNAs. In summary, this study analyzes the effect of known microRNAs in dendritic cells during fungal infections and proposes novel microRNAs that could be experimentally verified.
authors.affiliation: Systems Biology/Bioinformatics, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute Jena, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Dix
authors.affiliation: Department of Internal Medicine II, University Hospital of Würzburg Würzburg, Germany.
authors.forename: Kristin
authors.initials: K
authors.lastname: Czakai
authors.affiliation: Septomics Research Centre, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute, Friedrich Schiller UniversityJena, Germany; IMGM Laboratories GmbHMartinsried, Germany.
authors.forename: Ines
authors.initials: I
authors.lastname: Leonhardt
authors.affiliation: Institute of Medical Genetics and Applied Genomics, University of Tübingen Tübingen, Germany.
authors.forename: Karin
authors.initials: K
authors.lastname: Schäferhoff
authors.affiliation: IMGM Laboratories GmbH Martinsried, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Bonin
authors.affiliation: Systems Biology/Bioinformatics, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute Jena, Germany.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Guthke
authors.affiliation: Department of Internal Medicine II, University Hospital of Würzburg Würzburg, Germany.
authors.forename: Hermann
authors.initials: H
authors.lastname: Einsele
authors.affiliation: Septomics Research Centre, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute, Friedrich Schiller UniversityJena, Germany; Center for Sepsis Control and Care, University HospitalJena, Germany; Institute for Microbiology, University of WuerzburgWuerzburg, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Kurzai
authors.affiliation: Department of Internal Medicine II, University Hospital of Würzburg Würzburg, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Löffler
authors.affiliation: Systems Biology/Bioinformatics, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute Jena, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Linde
keywords: dendritic cells; fungal infection; ncRNA; novel microRNAs; pathogenic fungi; validated target genes