Helicobacter pylori down-regulates expression of human ß-defensin 1 in the gastric mucosa in a type IV secretion dependent fashion

Patel, S.R.; Smith, K.; Letley, D.P.; Cook, K.W.; Memon, A.A.; Ingram, R.J.M.; Staples, E.; Backert, S.; Zaltoun, A.M.; Atherton, J.C.; Robinson, K.

Abstract

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 (h?Ds) are antimicrobial peptides, h?D1 being constitutively expressed in the human stomach. We hypothesized that H. pylori may persist, in part, by downregulating gastric h?D1 expression. We measured h?D1 and h?D2 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 h?D1 and higher h?D2 mRNA and protein concentrations were present in gastric biopsies from infected patients. Those patients with higher-level bacterial colonization and inflammation had significantly lower h?D1 expression, but there were no differences in h?D2. H. pylori infection of human gastric epithelial cell lines also downregulated h?D1. Using wild-type strains and isogenic mutants, we showed that a functional cag pathogenicity island-encoded type IV secretion system induced this downregulation. Treatment with chemical inhibitors or siRNA revealed that H. pylori usurped NF-?B signalling to modulate h?D1 expression. These data indicate that H. pylori downregulates h?D1 expression via NF-?B signalling, and suggest that this may promote bacterial survival and persistence in the gastric niche.

Citation

Patel, S., Smith, K., Letley, D., Cook, K., Memon, A., Ingram, R., …Robinson, K. (2013). Helicobacter pylori down-regulates expression of human ß-defensin 1 in the gastric mucosa in a type IV secretion dependent fashion. Cellular Microbiology, 15(12), https://doi.org/10.1111/cmi.12174

• Journal Article Type: Article
• Publication Date: Aug 6, 2013
• Deposit Date: Apr 24, 2014
• Publicly Available Date: Apr 24, 2014
• Journal: Cellular Microbiology
• Print ISSN: 1462-5814
• Electronic ISSN: 1462-5814
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 15
• Issue: 12
• DOI: https://doi.org/10.1111/cmi.12174
• Public URL: https://nottingham-repository.worktribe.com/output/717224
• Publisher URL: http://onlinelibrary.wiley.com/doi/10.1111/cmi.12174/abstract