title: Muc1 mucin limits both Helicobacter pylori colonization of the murine gastric mucosa and associated gastritis.
abstract: OBJECTIVE
  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.affiliation: Mucosal Diseases Program, Mater Medical Research Institute and University of Queensland, Mater Misericordiae Hospitals, Brisbane, Australia.
authors.forename: Michael A
authors.initials: MA
authors.lastname: McGuckin
authors.forename: Alison L
authors.initials: AL
authors.lastname: Every
authors.forename: Caroline D
authors.initials: CD
authors.lastname: Skene
authors.forename: Sara K
authors.initials: SK
authors.lastname: Linden
authors.forename: Yok Teng
authors.initials: YT
authors.lastname: Chionh
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Swierczak
authors.forename: Julie
authors.initials: J
authors.lastname: McAuley
authors.forename: Stacey
authors.initials: S
authors.lastname: Harbour
authors.forename: Maria
authors.initials: M
authors.lastname: Kaparakis
authors.forename: Richard
authors.initials: R
authors.lastname: Ferrero
authors.forename: Philip
authors.initials: P
authors.lastname: Sutton
mesh_terms: D000818:Animals; D000917:Antibody Formation; D001422:Bacterial Adhesion; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D015169:Colony Count, Microbial; D004195:Disease Models, Animal; D005753:Gastric Mucosa / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D005756:Gastritis / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology / Q000517:prevention & control; D016481:Helicobacter Infections / Q000150:complications / Q000276:immunology / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D016480:Helicobacter pylori / Q000302:isolation & purification / Q000472:pathogenicity*; D006801:Humans; D007111:Immunity, Cellular; D051379:Mice; D018345:Mice, Knockout; D018396:Mucin-1 / Q000235:genetics / Q000378:metabolism*; D010295:Parietal Cells, Gastric / Q000378:metabolism / Q000382:microbiology; D011485:Protein Binding; D012720:Severity of Illness Index; D013997:Time Factors
chemical_list: D018396:Mucin-1