Cutting edge: Enhanced pulmonary clearance of Pseudomonas aeruginosa by Muc1 knockout mice

Wenju Lu, Akinori Hisatsune, Takeshi Koga, Kosuke Kato, Ippei Kuwahara, Erik P. Lillehoj, Wilbur Chen, Alan S. Cross, Sandra J Gendler, Andrew T. Gewirtz, K. Chul Kim

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Abstract

MUC1 (MUC1 in human and Muc1 in nonhumans) is a membrane-tethered mucin that interacts with Pseudomonas aeruginosa (PA) through flagellin. In this study, we compared PA pulmonary clearance and proinflammatory responses by Muc1-/- mice with Muc1+/+ litter-mates following intranasal instillation of PA or flagellin. Compared with Muc1+/+ mice, Muc1-/- mice showed increased PA clearance, greater airway recruitment of neutrophils, higher levels of TNF-α and KC in bronchoalveolar lavage fluid, higher levels of TNF-α in media of flagellin-stimulated alveolar macrophages, and higher levels of KC in media of tracheal epithelial cells. Knockdown of MUC1 enhanced flagellin-induced IL-8 production by primary human bronchial epithelial cells. Expression of MUC1 in HEK293T cells attenuated TLR5-dependent IL-8 release in response to flagellin, which was completely ablated when its cytoplasmic tail was deleted. We conclude that MUC1/Muc1 suppresses pulmonary innate immunity and speculate its antiinflammatory activity may play an important modulatory role during microbial infection.

Original languageEnglish (US)
Pages (from-to)3890-3894
Number of pages5
JournalJournal of Immunology
Volume176
Issue number7
StatePublished - Apr 1 2006

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ASJC Scopus subject areas

  • Immunology

Cite this

Lu, W., Hisatsune, A., Koga, T., Kato, K., Kuwahara, I., Lillehoj, E. P., Chen, W., Cross, A. S., Gendler, S. J., Gewirtz, A. T., & Kim, K. C. (2006). Cutting edge: Enhanced pulmonary clearance of Pseudomonas aeruginosa by Muc1 knockout mice. Journal of Immunology, 176(7), 3890-3894.