Muc1 Mucin Limits Both Helicobacter pylori Colonization of the Murine Gastric Mucosa and Associated Gastritis Academic Article uri icon

abstract

  • BACKGROUND & AIMS: The MUC1 mucin is expressed on the cell surface of epithelial cells lining the gastric mucosa. Epidemiologic studies suggest that functional allelic variations in the MUC1 gene may play a role in human susceptibility to Helicobacter pylori-associated pathologies, including gastric adenocarcinoma. We have evaluated the impact of Muc1 expression on the colonization and pathogenesis of gastric Helicobacter infections. METHODS: Wild-type and Muc1-deficient mice were infected with H pylori and colonization and gastritis levels determined. Primary gastric cells were used to examine the impact of Muc1 expression on bacterial adherence. RESULTS: Mice lacking Muc1 were colonized by 5-fold more H pylori within 1 day of infection, and this difference was maintained for at least 2 months postinfection. Mice heterozygous for the null Muc1 allele developed intermediate bacterial colonization. Although wild-type mice developed only a mild gastritis when infected for 2 months with H pylori, Muc1(-/-) mice developed an atrophic gastritis marked by loss of parietal cells. We demonstrate H pylori adhesion to purified MUC1 and significantly increased adhesion to cultured murine Muc1 null gastric epithelial cells, suggesting that Muc1 acts as a decoy limiting binding to the cell surface. CONCLUSIONS: Muc1 provides a protective barrier, which limits both acute and chronic colonization by H pylori, as well as playing a major role in limiting the inflammation induced by Helicobacter infection. We propose that Muc1 restricts access of H pylori to the epithelial surface, hence reducing exposure of the host to proinflammatory bacterial products.

authors

  • McGuckin, Michael A
  • Every, Alison L
  • Skene, Caroline D
  • Linden, Sara K
  • Chionh, Yok Teng
  • Swierczak, Agnieszka
  • McAuley, Julie
  • Harbour, Stacey
  • Kaparakis, Maria
  • Ferrero, Richard
  • Sutton, Philip

publication date

  • October 2007

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