title: Candida albicans infection leads to barrier breakdown and a MAPK/NF-κB mediated stress response in the intestinal epithelial cell line C2BBe1.
abstract: Intestinal epithelial cells (IEC) form a tight barrier to the gut lumen. Paracellular permeability of the intestinal barrier is regulated by tight junction proteins and can be modulated by microorganisms and other stimuli. The polymorphic fungus Candida albicans, a frequent commensal of the human mucosa, has the capacity of traversing this barrier and establishing systemic disease within the host. Infection of polarized C2BBe1 IEC with wild-type C. albicans led to a transient increase of transepithelial electric resistance (TEER) before subsequent barrier disruption, accompanied by a strong decline of junctional protein levels and substantial, but considerably delayed cytotoxicity. Time-resolved microarray-based transcriptome analysis of C. albicans challenged IEC revealed a prominent role of NF-κB and MAPK signalling pathways in the response to infection. Hence, we inferred a gene regulatory network based on differentially expressed NF-κB and MAPK pathway components and their predicted transcriptional targets. The network model predicted activation of GDF15 by NF-κB was experimentally validated. Furthermore, inhibition of NF-κB activation in C. albicans infected C2BBe1 cells led to enhanced cytotoxicity in the epithelial cells. Taken together our study identifies NF-κB activation as an important protective signalling pathway in the response of epithelial cells to C. albicans.
authors.affiliation: Septomics Research Centre, Friedrich Schiller University and Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute, Jena, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Böhringer
authors.affiliation: Septomics Research Centre, Friedrich Schiller University and Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute, Jena, Germany.
authors.forename: Susann
authors.initials: S
authors.lastname: Pohlers
authors.affiliation: Research Group Systems Biology and Bioinformatics, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute, Jena, Germany.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Schulze
authors.affiliation: BioControl Jena GmbH, Jena, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Albrecht-Eckardt
authors.affiliation: Septomics Research Centre, Friedrich Schiller University and Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute, Jena, Germany.
authors.forename: Judith
authors.initials: J
authors.lastname: Piegsa
authors.affiliation: Septomics Research Centre, Friedrich Schiller University and Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute, Jena, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Weber
authors.affiliation: Septomics Research Centre, Friedrich Schiller University and Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute, Jena, Germany.
authors.forename: Ronny
authors.initials: R
authors.lastname: Martin
authors.affiliation: Septomics Research Centre, Friedrich Schiller University and Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute, Jena, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Hünniger
authors.affiliation: Research Group Systems Biology and Bioinformatics, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute, Jena, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Linde
authors.affiliation: Research Group Systems Biology and 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: Septomics Research Centre, Friedrich Schiller University and Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute, Jena, Germany.|German National Reference Center for Invasive Fungal Infections, Hans Knöll Institute, Jena, Germany.
authors.forename: Oliver
authors.identifier: 0000-0002-6177-577X
authors.initials: O
authors.lastname: Kurzai
mesh_terms: D002176:Candida albicans / Q000472:pathogenicity*; D002177:Candidiasis / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D002460:Cell Line; D004847:Epithelial Cells / Q000378:metabolism / Q000382:microbiology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D054884:Host-Pathogen Interactions / Q000502:physiology*; D006801:Humans; D018928:Immunity, Mucosal / Q000235:genetics; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism / Q000382:microbiology; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D013312:Stress, Physiological / Q000502:physiology; D062725:Tight Junction Proteins / Q000378:metabolism
chemical_list: D016328:NF-kappa B; D062725:Tight Junction Proteins; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Candida albicans; MAP kinase; NF-κB; TEER; intestinaI epithelial barrier