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

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

Author information

1
Cystic Fibrosis/Pulmonary Research and Treatment Center, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. alessandra_livraghi@med.unc.edu

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.

PMID:
22419116
PMCID:
PMC3377774
DOI:
10.1038/mi.2012.17
[Indexed for MEDLINE]
Free PMC Article

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