Open AccessH elicobacter pylori downregulates expression of human β‐defensin 1 in the gastric mucosa in a type IV secretion‐dependent fashion
Author(s) -
Patel S. R.,
Smith K.,
Letley D. P.,
Cook K. W.,
Memon A. A.,
Ingram R. J. M.,
Staples E.,
Backert S.,
Zaitoun A. M.,
Atherton J. C.,
Robinson K.
Publication year - 2013
Publication title -
cellular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.542
H-Index - 138
eISSN - 1462-5822
pISSN - 1462-5814
DOI - 10.1111/cmi.12174
Subject(s) - secretion , biology , defensin , gastric mucosa , microbiology and biotechnology , endocrinology , stomach , biochemistry , antimicrobial
Summary 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 D 1 being constitutively expressed in the human stomach. We hypothesized that H . pylori may persist, in part, by downregulating gastric hβ D 1 expression. We measured hβ D 1 and hβ D 2 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 D 1 and higher hβ D 2 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 D 1 expression, but there were no differences in hβ D 2. H . pylori infection of human gastric epithelial cell lines also downregulated hβ D 1. 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 D 1 expression. These data indicate that H . pylori downregulates hβ D 1 expression via NF ‐κ B signalling, and suggest that this may promote bacterial survival and persistence in the gastric niche.