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 2017-11-01
Year available 2017
Sub-type Article (original research)
DOI 10.1038/mi.2017.16
Open Access Status Not yet assessed
Volume 10
Issue 6
Start page 1581
End page 1593
Total pages 13
Place of publication NEW YORK
Publisher NATURE PUBLISHING GROUP
Language eng
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
Pseudomonas-Aeruginosa
Tyrosine Phosphorylation
Mucosal Barrier
Mouse Model
Map Kinase
In-Vitro
Receptor
Glycoproteins
Inflammation
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID 1079924
1071916
DP120100194
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: WoS Import
 
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Created: Sun, 05 Nov 2017, 09:10:29 EST