MUC1 cell surface mucin is a critical element of the mucosal barrier to infection
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
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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Research Article Infectious disease

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

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 3

Muc1–/– mice are more susceptible to systemic infection by C. jejuni.

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Muc1–/– mice are more susceptible to systemic infection by C. jejuni. ...
Concentrations of C. jejuni in homogenized gastrointestinal and systemic tissues of Muc1–/– and Muc1+/+ 129/SvJ mice after oral inoculation with C. jejuni strain 81116. Mean ± SD of CFUs/g tissue. The colonization frequency (number of animals from which colonies were obtained/total number in the group) is shown at the base of each histogram (A, C, and D) or as pooled data for tissues and tissue types (B). (A) Six days after inoculation with 108 bacteria. (B) Four days after inoculation with 106, 104, 103, and 102 bacteria. (C) Two, 6, and 24 hours after inoculation with 104 bacteria. (D) Fourteen and 28 days after inoculation with 103 bacteria. (A and D) ANOVA, Tukey’s post-hoc test; (B and C) Mann-Whitney U test. *P < 0.05, Muc1–/– versus Muc1+/+; #P < 0.05, 14 days versus 28 days; **P < 0.01, Muc1–/– versus Muc1+/+; ##P < 0.01, 14 days versus 28 days; ***P < 0.001. C. jejuni was not detected in uninfected Muc1–/– and Muc1+/+ mice (not shown). GI, gastrointestinal.