RESUMO
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 (hßDs) are antimicrobial peptides, hßD1 being constitutively expressed in the human stomach. We hypothesized that H. pylori may persist, in part, by downregulating gastric hßD1 expression. We measured hßD1 and hßD2 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 hßD1 and higher hßD2 mRNA and protein concentrations were present in gastric biopsies from infected patients. Those patients with higher-level bacterial colonization and inflammation had significantly lower hßD1 expression, but there were no differences in hßD2. H. pylori infection of human gastric epithelial cell lines also downregulated hßD1. 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-κB signalling to modulate hßD1 expression. These data indicate that H. pylori downregulates hßD1 expression via NF-κB signalling, and suggest that this may promote bacterial survival and persistence in the gastric niche.
