Mucus clearance, MyD88-dependent and MyD88-independent immunity modulate lung susceptibility to spontaneous bacterial infection and inflammation

Mucosal Immunol. 2012 Jul;5(4):397-408. doi: 10.1038/mi.2012.17. Epub 2012 Mar 14.


It has been postulated that mucus stasis is central to the pathogenesis of obstructive lung diseases. In Scnn1b-transgenic (Scnn1b-Tg⁺ mice, airway-targeted overexpression of the epithelial Na⁺ channel β subunit causes airway surface dehydration, which results in mucus stasis and inflammation. Bronchoalveolar lavage from neonatal Scnn1b-Tg⁺ mice, but not wild-type littermates, contained increased mucus, bacteria, and neutrophils, which declined with age. Scnn1b-Tg⁺ mice lung bacterial flora included environmental and oropharyngeal species, suggesting inhalation and/or aspiration as routes of entry. Genetic deletion of the Toll-interleukin-1 receptor adapter molecule MyD88 in Scnn1b-Tg⁺ mice did not modify airway mucus obstruction, but caused defective neutrophil recruitment and increased bacterial infection, which persisted into adulthood. Scnn1b-Tg⁺ mice derived into germ-free conditions exhibited mucus obstruction similar to conventional Scnn1b-Tg⁺ mice and sterile inflammation. Collectively, these data suggest that dehydration-induced mucus stasis promotes infection, compounds defects in other immune mechanisms, and alone is sufficient to trigger airway inflammation.

Publication types

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

MeSH terms

  • Animals
  • Bacterial Infections / genetics
  • Bacterial Infections / immunology
  • Disease Models, Animal
  • Epithelial Sodium Channels / genetics
  • Lung / immunology*
  • Lung / metabolism*
  • Lung / microbiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Mucus / metabolism*
  • Myeloid Differentiation Factor 88 / metabolism*
  • Neutrophils / immunology
  • Pneumonia / immunology*
  • Pneumonia / metabolism*
  • Pneumonia / microbiology
  • Signal Transduction


  • Epithelial Sodium Channels
  • Myeloid Differentiation Factor 88
  • Scnn1b protein, mouse