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MUC1 cell surface mucin is a critical element of the mucosal barrier to infection
Julie L. McAuley, … , Victoria Korolik, Michael A. McGuckin
Julie L. McAuley, … , Victoria Korolik, Michael A. McGuckin
Published August 1, 2007
Citation Information: J Clin Invest. 2007;117(8):2313-2324. https://doi.org/10.1172/JCI26705.
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Research Article Infectious disease Article has an altmetric score of 8

MUC1 cell surface mucin is a critical element of the mucosal barrier to infection

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Abstract

Cell surface mucin glycoproteins are highly expressed by all mucosal tissues, yet their physiological role is currently unknown. We hypothesized that cell surface mucins protect mucosal cells from infection. A rapid progressive increase in gastrointestinal expression of mucin 1 (Muc1) cell surface mucin followed infection of mice with the bacterial pathogen Campylobacter jejuni. In the first week following oral infection, C. jejuni was detected in the systemic organs of the vast majority of Muc1–/– mice but never in Muc1+/+ mice. Although C. jejuni entered gastrointestinal epithelial cells of both Muc1–/– and Muc1+/+ mice, small intestinal damage as manifested by increased apoptosis and enucleated and shed villous epithelium was more common in Muc1–/– mice. Using radiation chimeras, we determined that prevention of systemic infection in wild-type mice was due exclusively to epithelial Muc1 rather than Muc1 on hematopoietic cells. Expression of MUC1-enhanced resistance to C. jejuni cytolethal distending toxin (CDT) in vitro and CDT null C. jejuni showed lower gastric colonization in Muc1–/– mice in vivo. We believe this is the first in vivo experimental study to demonstrate that cell surface mucins are a critical component of mucosal defence and that the study provides the foundation for exploration of their contribution to epithelial infectious and inflammatory diseases.

Authors

Julie L. McAuley, Sara K. Linden, Chin Wen Png, Rebecca M. King, Helen L. Pennington, Sandra J. Gendler, Timothy H. Florin, Geoff R. Hill, Victoria Korolik, Michael A. McGuckin

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Figure 6

Reduced bacterial flora increases susceptibility of Muc1+/+ mice to C. jejuni infection, but bacterial flora is not altered in Muc1–/– mice.

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Reduced bacterial flora increases susceptibility of Muc1+/+ mice to C. j...
(A) Concentrations of C. jejuni in gastrointestinal and systemic tissues of Muc1–/– and Muc1+/+ 129/SvJ mice after oral inoculation with 105C. jejuni strain 81116 with (+) and without (–) treatment with broad spectrum oral antibiotics for 7 days. Antibiotics were withdrawn 24 hours prior to inoculation. Mean ± SD of CFUs/g tissue. Colonization frequency is shown at the base of each histogram. ANOVA, Tukey’s post-hoc test; *P < 0.05, Muc1–/– versus Muc1+/+; ***P < 0.001, Muc1–/– versus Muc1+/+; †P < 0.001, antibiotics versus control. (B) Number of bacteria in the entire large intestine was estimated by counting SYBR green–stained bacteria on filtered fixed tissue homogenates. DNA was extracted from feces of Muc1–/– and Muc1+/+ mice and quantitative PCR used to amplify 16S ribosomal DNA and quantify the abundance of major intestinal bacterial groups. BPP, Bacteroides-Prevotella-Porphyromonas group; Ccoc, C. coccoides group; Entero, Enterococcus spp; Lacto, Lactobacillus group; Desulfo, Desulfovibrio group; Clep, C. leptum subgroup; Bifido, Bifidobacterium genus. Results in individual mice were expressed as a proportion of the result for universal bacterial 16S ribosomal DNA primers. Box plots show medians, quartiles, and ranges.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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