Elsevier

Mucosal Immunology

Volume 5, Issue 4, July 2012, Pages 397-408
Mucosal Immunology

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

https://doi.org/10.1038/mi.2012.17Get rights and content
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Abstract

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.

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Published online: 14 3 2012

Supplementary information The online version of this article (doi:10.1038/mi.2012.17) contains supplementary material, which is available to authorized users.