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

McAuley, Julie L., Linden, Sara K., Png, Chin Wen, King, Rebecca M., Pennington, Helen L., Gendler, Sandra J., Florin, Timothy H., Hill, Geoff R., Korolik, Victoria and McGuckin, Michael A. (2007) MUC1 cell surface mucin is a critical element of the mucosal barrier to infection. Journal of Clinical Investigation, 117 8: 2313-2324. doi:10.1172/JCI26705


Author McAuley, Julie L.
Linden, Sara K.
Png, Chin Wen
King, Rebecca M.
Pennington, Helen L.
Gendler, Sandra J.
Florin, Timothy H.
Hill, Geoff R.
Korolik, Victoria
McGuckin, Michael A.
Title MUC1 cell surface mucin is a critical element of the mucosal barrier to infection
Journal name Journal of Clinical Investigation   Check publisher's open access policy
ISSN 0021-9738
Publication date 2007-01-01
Sub-type Article (original research)
DOI 10.1172/JCI26705
Volume 117
Issue 8
Start page 2313
End page 2324
Total pages 12
Place of publication United States
Publisher American Society for Clinical Investigation
Language eng
Subject C1
321010 Infectious Diseases
321011 Medical Genetics
730101 Infectious diseases
Formatted 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.
Keyword Medicine, Research & Experimental
Q-Index Code C1
Q-Index Status Confirmed Code

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
2008 Higher Education Research Data Collection
School of Medicine Publications
 
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Created: Fri, 18 Apr 2008, 23:39:57 EST by Maree Knight on behalf of School of Medicine