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

J Immunol. 2006 Apr 1;176(7):3890-4. doi: 10.4049/jimmunol.176.7.3890.


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(+/+) littermates 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-alpha and KC in bronchoalveolar lavage fluid, higher levels of TNF-alpha 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 anti-inflammatory activity may play an important modulatory role during microbial infection.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Cytokines / biosynthesis
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Flagellin / pharmacology
  • Gene Deletion
  • Gene Expression Regulation / drug effects
  • Humans
  • Inflammation Mediators / metabolism
  • Lung / immunology*
  • Lung / microbiology*
  • Mice
  • Mice, Knockout
  • Mucin-1 / genetics*
  • Mucin-1 / metabolism*
  • Pneumonia, Bacterial / genetics
  • Pneumonia, Bacterial / immunology
  • Pneumonia, Bacterial / microbiology
  • Pseudomonas Infections / genetics
  • Pseudomonas Infections / immunology*
  • Pseudomonas Infections / microbiology*
  • Pseudomonas aeruginosa / immunology*
  • RNA, Small Interfering / genetics
  • Toll-Like Receptor 5 / metabolism


  • Cytokines
  • Inflammation Mediators
  • Mucin-1
  • RNA, Small Interfering
  • Toll-Like Receptor 5
  • Flagellin