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

H elicobacter 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 (hβ Ds) are antimicrobial peptides, hβ D1 being constitutively expressed in the human stomach. We hypothesized that H . pylori may persist, in part, by downregulating gastric hβ D1 expression. We measured hβ D1 and hβ 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 hβ D1 and higher hβ 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 hβ D1 expression, but there were no differences in hβ D2. H . pylori infection of human gastric epithelial cell lines also downregulated hβ 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-κ B signalling to modulate hβ D1 expression. These data indicate that H . pylori downregulates hβ D1 expression via NF-κ B signalling, and suggest that this may promote bacterial survival and persistence in the gastric niche. [ABSTRACT FROM AUTHOR]