title: Induction of the NFκ-B signal transduction pathway in response to Corynebacterium diphtheriae infection.
abstract: Corynebacterium diphtheriae, the causative agent of diphtheria, has been thoroughly studied with respect to toxin production and pili formation, while knowledge on host responses to C. diphtheriae infection is limited. In this study, we studied adhesion to and invasion of epithelial cells by different C. diphtheriae isolates. When NFκ-B reporter cell lines were used to monitor the effect of C. diphtheriae infection on human cells, strain-specific differences were observed. While adhesion to host cells had no effect, a correlation of invasion rate with NFκ-B induction was found, which indicates that internalization of bacteria is crucial for NFκ-B induction. Immunofluorescence microscopy experiments used to support the reporter assays showed that translocation of p65, as a hallmark of NFκ-B induction, was only observed in association with cell invasion by C. diphtheriae. Our data indicate that the response of epithelial cells to C. diphtheriae infection is determined by internalization of bacteria and that invasion of these cells is an active process; tetracycline-treated C. diphtheriae was still able to attach to host cells, but lost its ability to invade the cytoplasm. Recognition of pathogen-associated molecular patterns such as pili subunits by membrane-bound receptors facing the outside of the cell is not sufficient for NFκ-B induction.
authors.affiliation: Friedrich-Alexander-Universität Erlangen-Nürnberg, Lehrstuhl für Mikrobiologie, Staudtstr. 5, 91058 Erlangen, Germany.
authors.forename: Lisa
authors.initials: L
authors.lastname: Ott
authors.affiliation: Klinische und Molekulare Virologie, Virologisches Institut des Universitätsklinikums Erlangen, Schlossgarten 4, 91054, Erlangen, Germany.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Scholz
authors.affiliation: Friedrich-Alexander-Universität Erlangen-Nürnberg, Lehrstuhl für Mikrobiologie, Staudtstr. 5, 91058 Erlangen, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Höller
authors.affiliation: BioCer Entwicklungs-GmbH, Ludwig-Thoma-Str. 36c, 95447 Bayreuth, Germany.
authors.forename: Kristin
authors.initials: K
authors.lastname: Hasselt
authors.affiliation: Klinische und Molekulare Virologie, Virologisches Institut des Universitätsklinikums Erlangen, Schlossgarten 4, 91054, Erlangen, Germany.
authors.forename: Armin
authors.initials: A
authors.lastname: Ensser
authors.affiliation: Friedrich-Alexander-Universität Erlangen-Nürnberg, Lehrstuhl für Mikrobiologie, Staudtstr. 5, 91058 Erlangen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Burkovski
mesh_terms: D001422:Bacterial Adhesion; D002460:Cell Line; D003353:Corynebacterium diphtheriae / Q000276:immunology* / Q000472:pathogenicity; D004705:Endocytosis; D004847:Epithelial Cells / Q000382:microbiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D016328:NF-kappa B / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D016328:NF-kappa B