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

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 2

C. jejuni adheres to murine intestinal mucins and the H type 2 oligosaccharide and binds more rapidly to MUC1-expressing cells.

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C. jejuni adheres to murine intestinal mucins and the H type 2 oligosac...
ELISA results showing (A) binding of C. jejuni strain 81116 to mucin purified from murine small intestine and BSA (control for nonspecific binding) at pH 7.2 and 6.0 and (B) binding at pH 7.2–5.0 both without (control) and with prior desialylation of mucin with neuraminidase. (C) Binding of mucin oligosaccharides conjugated to FITC-labeled human serum albumin to C. jejuni. Fluorescence units are shown after deducting mean background autofluorescence of the C. jejuni alone. sLex, sialyl-Lex; H2, H type 2. (D) MUC1 expression determined by flow cytometry in 2 independent stable clones established from HCT116 intestinal cancer cells transfected with MUC1 (MUC1.A and MUC1.B) and 2 independent stable clones from the pcDNA3 vector (Vector.A and Vector.B) (shaded area is negative control antibody; dark line is BC2 antibody reactive with the extracellular domain of MUC1). Clones were cocultured with 106C. jejuni per well for 1 or 2 hours under microaerophilic conditions. Adhesion of C. jejuni was determined at 1 and 2 hours, and invasion was determined at 2 hours only. Mean ± SD is shown. (A) ***P < 0.001 versus BSA; ###P < 0.001 versus pH 7.2; (B) *P < 0.05; **P < 0.01 versus control; (C) ***P < 0.001 versus albumin-FITC; ANOVA and Tukey’s post-hoc test were used. (D) Box plots showing medians, quartiles, and ranges are shown.