Helicobacter pylori downregulates expression of human β-defensin 1 in the gastric mucosa in a type IV secretion-dependent fashion

Authors

  • S. R. Patel,

    1. Nottingham Digestive Diseases Biomedical Research Unit, University of Nottingham, Nottingham, UK
    2. Centre for Biomolecular Sciences, University of Nottingham, Nottingham, UK
    Search for more papers by this author
  • K. Smith,

    1. Nottingham Digestive Diseases Biomedical Research Unit, University of Nottingham, Nottingham, UK
    2. Centre for Biomolecular Sciences, University of Nottingham, Nottingham, UK
    Search for more papers by this author
  • D. P. Letley,

    1. Nottingham Digestive Diseases Biomedical Research Unit, University of Nottingham, Nottingham, UK
    2. Centre for Biomolecular Sciences, University of Nottingham, Nottingham, UK
    Search for more papers by this author
  • K. W. Cook,

    1. Nottingham Digestive Diseases Biomedical Research Unit, University of Nottingham, Nottingham, UK
    2. Centre for Biomolecular Sciences, University of Nottingham, Nottingham, UK
    Search for more papers by this author
  • A. A. Memon,

    1. Nottingham Digestive Diseases Biomedical Research Unit, University of Nottingham, Nottingham, UK
    2. Centre for Biomolecular Sciences, University of Nottingham, Nottingham, UK
    Search for more papers by this author
  • R. J. M. Ingram,

    1. Nottingham Digestive Diseases Biomedical Research Unit, University of Nottingham, Nottingham, UK
    2. Centre for Biomolecular Sciences, University of Nottingham, Nottingham, UK
    Search for more papers by this author
  • E. Staples,

    1. Nottingham Digestive Diseases Biomedical Research Unit, University of Nottingham, Nottingham, UK
    2. Centre for Biomolecular Sciences, University of Nottingham, Nottingham, UK
    Search for more papers by this author
  • S. Backert,

    1. Lehrstuhl für Mikrobiologie, Department für Biologie, Friedrich-Alexander-Universität Erlangen Nürnberg, Erlangen, Germany
    Search for more papers by this author
  • A. M. Zaitoun,

    1. Department of Cellular Pathology, Nottingham University Hospitals NHS Trust, Nottingham, UK
    Search for more papers by this author
  • J. C. Atherton,

    1. Nottingham Digestive Diseases Biomedical Research Unit, University of Nottingham, Nottingham, UK
    2. Centre for Biomolecular Sciences, University of Nottingham, Nottingham, UK
    Search for more papers by this author
  • K. Robinson

    Corresponding author
    1. Nottingham Digestive Diseases Biomedical Research Unit, University of Nottingham, Nottingham, UK
    2. Centre for Biomolecular Sciences, University of Nottingham, Nottingham, UK
    Search for more papers by this author

Summary

Helicobacter pylori establishes a chronic lifelong infection in the human gastric mucosa, which may lead to peptic ulcer disease or gastric adenocarcinoma. The human beta-defensins (hβDs) are antimicrobial peptides, hβD1 being constitutively expressed in the human stomach. We hypothesized that H. pylori may persist, in part, by downregulating gastric hβD1 expression. We measured hβD1 and hβD2 expression in vivo in relation to the presence, density and severity of H. pylori infection, investigated differential effects of H. pylori virulence factors, and studied underlying signalling mechanisms in vitro. Significantly lower hβD1 and higher hβD2 mRNA and protein concentrations were present in gastric biopsies from infected patients. Those patients with higher-level bacterial colonization and inflammation had significantly lower hβD1 expression, but there were no differences in hβD2. H. pylori infection of human gastric epithelial cell lines also downregulated hβD1. Using wild-type strains and isogenic mutants, we showed that a functionalcag pathogenicity island-encoded type IV secretion system induced this downregulation. Treatment with chemical inhibitors or siRNA revealed that H. pylori usurped NF-κB signalling to modulate hβD1 expression. These data indicate that H. pylori downregulates hβD1 expression via NF-κB signalling, and suggest that this may promote bacterial survival and persistence in the gastric niche.

Ancillary