The cell surface mucin MUC1 limits the severity of influenza A virus infection

McAuley, J. L., Corcilius, L., Tan, H. -X., Payne, R. J., McGuckin, M. A. and Brown, L. E. (2017) The cell surface mucin MUC1 limits the severity of influenza A virus infection. Mucosal Immunology, 10 6: 1581-1593. doi:10.1038/mi.2017.16

Author McAuley, J. L.
Corcilius, L.
Tan, H. -X.
Payne, R. J.
McGuckin, M. A.
Brown, L. E.
Title The cell surface mucin MUC1 limits the severity of influenza A virus infection
Journal name Mucosal Immunology   Check publisher's open access policy
ISSN 1933-0219
Publication date 2017-03-22
Year available 2017
Sub-type Article (original research)
DOI 10.1038/mi.2017.16
Open Access Status DOI
Volume 10
Issue 6
Start page 1581
End page 1593
Total pages 13
Place of publication New York, NY, United States
Publisher Nature Publishing Group
Language eng
Subject 2723 Immunology and Allergy
2403 Immunology
Abstract Cell surface mucin (cs-mucin) glycoproteins are constitutively expressed at the surface of respiratory epithelia where pathogens such as influenza A virus (IAV) gain entry into cells. Different members of the cs-mucin family each express a large and heavily glycosylated extracellular domain that towers above other receptors on the epithelial cell surface, a transmembrane domain that enables shedding of the extracellular domain, and a cytoplasmic tail capable of triggering signaling cascades. We hypothesized that IAV can interact with the terminal sialic acids presented on the extracellular domain of cs-mucins, resulting in modulation of infection efficiency. Utilizing human lung epithelial cells, we found that IAV associates with the cs-mucin MUC1 but not MUC13 or MUC16. Overexpression of MUC1 by epithelial cells or the addition of sialylated synthetic MUC1 constructs, reduced IAV infection in vitro. In addition, Muc1(-/-) mice infected with IAV exhibited enhanced morbidity and mortality, as well as greater inflammatory mediator responses compared to wild type mice. This study implicates the cs-mucin MUC1 as a critical and dynamic component of the innate host response that limits the severity of influenza and provides the foundation for exploration of MUC1 in resolving inflammatory disease.
Keyword Airway Epithelial-Cells
Tyrosine Phosphorylation
Mucosal Barrier
Mouse Model
Map Kinase
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID 1079924
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Mater Research Institute-UQ (MRI-UQ)
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Created: Sun, 05 Nov 2017, 09:10:29 EST