title: Krüppel-like Factor 4 modulates interleukin-6 release in human dendritic cells after in vitro stimulation with Aspergillus fumigatus and Candida albicans.
abstract: Invasive fungal infections are associated with high mortality rates and are mostly caused by the opportunistic fungi Aspergillus fumigatus and Candida albicans. Immune responses against these fungi are still not fully understood. Dendritic cells (DCs) are crucial players in initiating innate and adaptive immune responses against fungal infections. The immunomodulatory effects of fungi were compared to the bacterial stimulus LPS to determine key players in the immune response to fungal infections. A genome wide study of the gene regulation of human monocyte-derived dendritic cells (DCs) confronted with A. fumigatus, C. albicans or LPS was performed and Krüppel-like factor 4 (KLF4) was identified as the only transcription factor that was down-regulated in DCs by both fungi but induced by stimulation with LPS. Downstream analysis demonstrated the influence of KLF4 on the interleukine-6 expression in human DCs. Furthermore, KLF4 regulation was shown to be dependent on pattern recognition receptor ligation. Therefore KLF4 was identified as a controlling element in the IL-6 immune response with a unique expression pattern comparing fungal and LPS stimulation.
authors.affiliation: University Hospital of Würzburg, Department of Internal Medicine II, WÜ4i, Würzburg, Germany.
authors.forename: Kristin
authors.initials: K
authors.lastname: Czakai
authors.affiliation: Septomics Research Centre, Friedrich Schiller University and Leibniz Institute for Natural Product Research and Infection Biology-Hans-Knöll-Institute (HKI), Jena, Germany.
authors.forename: Ines
authors.initials: I
authors.lastname: Leonhardt
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: Institute of Medical Genetics and Applied Genomics, University of Tübingen, Tübingen, 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: Joerg
authors.initials: J
authors.lastname: Linde
authors.affiliation: University Hospital of Würzburg, Department of Internal Medicine II, WÜ4i, Würzburg, Germany.
authors.forename: Hermann
authors.initials: H
authors.lastname: Einsele
authors.affiliation: Septomics Research Centre, Friedrich Schiller University and Leibniz Institute for Natural Product Research and Infection Biology-Hans-Knöll-Institute (HKI), Jena, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Kurzai
authors.affiliation: University Hospital of Würzburg, Department of Internal Medicine II, WÜ4i, Würzburg, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Loeffler
mesh_terms: D001228:Aspergillosis / Q000276:immunology / Q000401:mortality / Q000473:pathology; D001232:Aspergillus fumigatus / Q000276:immunology*; D002176:Candida albicans / Q000276:immunology*; D002460:Cell Line; D003713:Dendritic Cells / Q000276:immunology*; D020869:Gene Expression Profiling; D006801:Humans; D015850:Interleukin-6 / Q000276:immunology* / Q000378:metabolism; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000276:immunology; D055732:Pulmonary Aspergillosis / Q000276:immunology / Q000401:mortality / Q000473:pathology; D051192:Receptors, Pattern Recognition / Q000378:metabolism*
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6; C000715467:KLF4 protein, human; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D008070:Lipopolysaccharides; D051192:Receptors, Pattern Recognition