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 (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.
Highlights
Helicobacter pylori persistently infects the stomachs of almost half the world’s population
Helicobacter pylori establishes a chronic lifelong infection in the human gastric mucosa, which may lead to peptic ulcer disease or gastric adenocarcinoma
We hypothesized that H. pylori may persist, in part, by downregulating gastric hβD1 expression
Summary
Helicobacter pylori persistently infects the stomachs of almost half the world’s population. Once translocated into the cytosol, CagA activates specific signalling pathways, including MAP kinase and NF-κBinduced signalling. Both NF-κB p50/p65 heterodimers and p65 or p50 homodimers undergo nuclear translocation (Keates et al, 1997; Wada et al, 2001; Saha et al, 2008). The cagPAI allows translocation of soluble bacterial cell wall components into the epithelial cytosol. These short-chain peptidoglycan derivatives (disaccharide tripeptides) are generated via activity of the lytic transglycosylase encoded by slt (HP0645), an enzyme normally involved in peptidoglycan remodelling. The disaccharide tripeptides are recognized by nucleotide-binding oligomerization domain 1 (NOD1), an intracellular sensor of Gram-
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
