Muc1 mucin limits both Helicobacter pylori colonization of the murine gastric mucosa and associated gastritis.
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.
McGuckin
Michael A
MA
Mucosal Diseases Program, Mater Medical Research Institute and University of Queensland, Mater Misericordiae Hospitals, Brisbane, Australia.
Every
Alison L
AL
Skene
Caroline D
CD
Linden
Sara K
SK
Chionh
Yok Teng
YT
Swierczak
Agnieszka
A
McAuley
Julie
J
Harbour
Stacey
S
Kaparakis
Maria
M
Ferrero
Richard
R
Sutton
Philip
P
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
D018396:Mucin-1