Muc1 Mucin Limits Both Helicobacter pylori Colonization of the Murine Gastric Mucosa and Associated Gastritis

• Published in: Gastroenterology (New York, N.Y. 1943) Vol. 133; no. 4; pp. 1210 - 1218
• Main 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
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-10-2007
• Subjects: Animals; Antibody Formation; Bacterial Adhesion; Cell Line, Tumor; Cells, Cultured; Colony Count, Microbial; Disease Models, Animal; Gastric Mucosa - metabolism; Gastric Mucosa - microbiology; Gastric Mucosa - pathology; Gastritis - metabolism; Gastritis - microbiology; Gastritis - pathology; Gastritis - prevention & control; Gastroenterology and Hepatology; Helicobacter Infections - complications; Helicobacter Infections - immunology; Helicobacter Infections - metabolism; Helicobacter Infections - microbiology; Helicobacter Infections - pathology; Helicobacter pylori - isolation & purification; Helicobacter pylori - pathogenicity; Humans; Immunity, Cellular; Mice; Mice, Knockout; Mucin-1 - genetics; Mucin-1 - metabolism; Parietal Cells, Gastric - metabolism; Parietal Cells, Gastric - microbiology; Protein Binding; Severity of Illness Index; Time Factors; RT; room temperature
• ISSN: 0016-5085; 1528-0012
• DOI: 10.1053/j.gastro.2007.07.003

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.