title: The Cytolethal Distending Toxin Subunit CdtB of Helicobacter Induces a Th17-related and Antimicrobial Signature in Intestinal and Hepatic Cells In Vitro.
abstract: Enterohepatic Helicobacter species are associated with several digestive diseases. Helicobacter pullorum is an emerging human foodborne pathogen, and Helicobacter hepaticus is a mouse pathogen; both species are associated with intestinal and/or hepatic diseases. They possess virulence factors, such as cytolethal distending toxin (CDT). Data indicate that CDT may be involved in chronic inflammatory responses, via its active subunit, CdtB. The proinflammatory properties of the CdtB of H. pullorum and H. hepaticus were assessed on human intestinal and hepatic epithelial cells in vitro. Interleukin 8 expression was evaluated by using wild-type strains and their corresponding CdtB isogenic mutants and by delivering CdtB directly into the cells. Nuclear factor κB nuclear translocation and transcriptomic characteristics in response to CdtB were also evaluated. The CdtB of these Helicobacter species induced nuclear factor κB nuclear translocation and exhibited proinflammatory properties, mainly the expression of T-helper type 17-related genes and genes encoding antimicrobial products also involved in cancer. The Histidine residue in position 265 of the CdtB catalytic site appeared to play a role in the regulation of most of these genes. As for flagellin or lipopolysaccharides, CdtB also induced expression of inflammation-associated genes related to antimicrobial activity.
authors.affiliation: Université de Bordeaux, Laboratoire de bactériologie, UMR1053 INSERM UMR1053, Bordeaux Research in Translational Oncology, BaRITOn.
authors.forename: Christelle
authors.initials: C
authors.lastname: Péré-Védrenne
authors.affiliation: Université de Bordeaux, Biothérapies des maladies génétiques et cancers, INSERM U1035 Bordeaux Institut National Polytechnique, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Cardinaud
authors.affiliation: Université de Bordeaux, Laboratoire de bactériologie, UMR1053 INSERM UMR1053, Bordeaux Research in Translational Oncology, BaRITOn.
authors.forename: Christine
authors.initials: C
authors.lastname: Varon
authors.affiliation: Université de Bordeaux, Laboratoire de bactériologie, UMR1053 INSERM UMR1053, Bordeaux Research in Translational Oncology, BaRITOn.
authors.forename: Iulia
authors.initials: I
authors.lastname: Mocan
authors.affiliation: Université de Bordeaux, Laboratoire de bactériologie, UMR1053 INSERM UMR1053, Bordeaux Research in Translational Oncology, BaRITOn.
authors.forename: Alice
authors.initials: A
authors.lastname: Buissonnière
authors.affiliation: Université de Bordeaux, Laboratoire de bactériologie, UMR1053 INSERM UMR1053, Bordeaux Research in Translational Oncology, BaRITOn.
authors.forename: Julien
authors.initials: J
authors.lastname: Izotte
authors.affiliation: Université de Bordeaux, Laboratoire de bactériologie, UMR1053 INSERM UMR1053, Bordeaux Research in Translational Oncology, BaRITOn.
authors.forename: Francis
authors.initials: F
authors.lastname: Mégraud
authors.affiliation: Université de Bordeaux, Laboratoire de bactériologie, UMR1053 INSERM UMR1053, Bordeaux Research in Translational Oncology, BaRITOn.
authors.forename: Armelle
authors.initials: A
authors.lastname: Ménard
mesh_terms: D000890:Anti-Infective Agents / Q000276:immunology*; D001427:Bacterial Toxins / Q000235:genetics / Q000276:immunology*; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000276:immunology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D016998:Helicobacter / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D016481:Helicobacter Infections / Q000276:immunology* / Q000382:microbiology; D022781:Hepatocytes / Q000276:immunology; D006801:Humans; D016209:Interleukin-8 / Q000276:immunology; D007422:Intestines / Q000276:immunology; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D058504:Th17 Cells / Q000276:immunology; D037521:Virulence Factors
chemical_list: D000890:Anti-Infective Agents; D001427:Bacterial Toxins; D016209:Interleukin-8; D037521:Virulence Factors; C067044:cytolethal distending toxin
keywords: CDT; Helicobacter hepaticus; Helicobacter pullorum; inflammation; kallikrein KLK5 KLK7; microarray