Gastroenterology

Gastroenterology

Volume 133, Issue 4, October 2007, Pages 1210-1218
Gastroenterology

Basic–alimentary tract
Muc1 Mucin Limits Both Helicobacter pylori Colonization of the Murine Gastric Mucosa and Associated Gastritis

https://doi.org/10.1053/j.gastro.2007.07.003Get rights and content

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.

Section snippets

Bacterial Culture

H pylori strains SS1,5 B128, and J99 (kindly provided by Thomas Boren, Umeå University, Sweden) were initially grown on horse blood agar plates (Blood Agar Base No. 2, 0.02% Amphostat, and Skirrow’s Selective Supplements [Oxoid, Basingstoke, United Kingdom] and 5% horse blood [Biolab, Clayton, Australia]) in an anaerobic jar with a microaerophilic gas generating kit (Oxoid) for 2 days at 37°C. For infection of mice and primary cell culture adhesion assays, H pylori were cultured in brain heart

Expression of Muc1 Limits Both Acute and Chronic Colonization by H pylori

To examine the effect of Muc1 expression on colonization by gastric Helicobacters, Muc1+/+ and Muc1−/− mice were infected with H pylori-SS1 for 1 day or 1, 2, or 8 weeks before sampling of gastric tissues. Significantly, H pylori colonization in Muc1−/− mice was consistently higher compared with Muc1+/+ wild-type controls at each time point (Figure 1). The elevation in bacterial burden in the Muc1-deficient animals was remarkably constant, being between 3- to 5-fold higher from 1 day through to

Discussion

The majority of human pathogens either colonize or invade the body via a mucosal surface. The mucosal interface thus provides the first-line defensive barrier against many infections. Mucins are thought to be key components of this defense, although there is minimal experimental in vivo evidence for this dogma. Some mucins, because of their gel-forming properties, are the primary constituents of the mucus that coats mucosal surfaces, whereas others are attached to the apical surface of the

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    The authors have no conflicts of interest to disclose.

    Supported by Australian NHMRC Project Grants 235608 and 382309, Queensland Cancer Fund Senior Research Fellowship (to M.M.), and Australian NHMRC Project Grant 350375 (to P.S.).

    1

    M.M. and A.E. contributed equally to this work.

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