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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.

Authors

S.R. Patel

K. Smith

D.P. Letley

K.W. Cook

A.A. Memon

R.J.M. Ingram

E. Staples

S. Backert

A.M. Zaltoun

J.C. Atherton

K. Robinson

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 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 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.

Journal Article Type Article
Publication Date Aug 6, 2013
Journal Cellular Microbiology
Print ISSN 1462-5814
Electronic ISSN 1462-5814
Publisher Wiley
Peer Reviewed Peer Reviewed
Volume 15
Issue 12
Institution 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), doi:10.1111/cmi.12174
DOI https://doi.org/10.1111/cmi.12174
Publisher URL http://onlinelibrary.wiley.com/doi/10.1111/cmi.12174/abstract
Copyright Statement Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0

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Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0




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