Candida albicans infection leads to barrier breakdown and a MAPK/NF‐κB mediated stress response in the intestinal epithelial cell line C2BBe1. (26th February 2016)

• Record Type: Journal Article
• Authors: Böhringer, Michael; Pohlers, Susann; Schulze, Sylvie; Albrecht‐Eckardt, Daniela; Piegsa, Judith; Weber, Michael; Martin, Ronny; Hünniger, Kerstin; Linde, Jörg; Guthke, Reinhard; Kurzai, Oliver
• Is Part Of: Cellular microbiology. Volume 18:Number 7(2016)
• Page Start: 889
• Page End: 904
• Publication Date: 2016-02-26
• Subjects: intestinaI epithelial barrier -- TEER -- Candida albicans -- NF‐κB -- MAP kinase; Microbiology -- Periodicals; Cytology -- Periodicals; Host-parasite relationships -- Periodicals; Microbiology -- Periodicals; Cells -- Periodicals; Microbiologie -- Périodiques; Microbiologie; Relation hôte-parasite; Cytologie; Cellule; Réponse cellulaire; Ressource Internet (Descripteur de forme); Périodique électronique (Descripteur de forme); 579.05
• DOI: 10.1111/cmi.12566
• Languages: English
• ISSNs: 1462-5814

Abstract

Summary: 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 . Abstract : Intestinal barrier breakdown is an important prerequisite for invasive Candida albicans infection resulting from intestinal colonization. In their study, Böhringer et al. analyze time resolved data on barrier breakdown and transcriptomic changes and identify NF‐κB as a central hub in the epithelial cells' response to C. albicans activation. Upon infection, NF‐κB signaling mediates barrier protection and is central for a protective signaling pathway in the response of epithelial cells to C. albicans .