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*
Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115; and
Department of Anesthesiology and Critical Care Medicine, University of Tuebingen, Tuebingen, Germany
The cystic fibrosis (CF) transmembrane conductance regulator (CFTR)
has been proposed to be an epithelial cell receptor for
Pseudomonas aeruginosa involved in bacterial
internalization and clearance from the lung. We evaluated the role of
CFTR in clearing P. aeruginosa from the respiratory
tract using transgenic CF mice that carried either the 
F508
Cftr allele or an allele with a Cftr stop
codon (S489X). Intranasal application achieved P.
aeruginosa lung infection in inbred C57BL/6 F508
Cftr mice, whereas F508 Cftr and S489X
Cftr outbred mice required tracheal application of the
inoculum to establish lung infection. CF mice showed significantly less
ingestion of LPS-smooth P. aeruginosa by lung cells and
significantly greater bacterial lung burdens 4.5 h postinfection
than C57BL/6 wild-type mice. Microscopy of infected mouse and rhesus
monkey tracheas clearly demonstrated ingestion of P.
aeruginosa by epithelial cells in wild-type animals, mostly
around injured areas of the epithelium. Desquamating cells loaded with
P. aeruginosa could also be seen in these tissues. No
difference was found between CF and wild-type mice challenged with an
LPS-rough mucoid isolate of P. aeruginosa lacking the
CFTR ligand. Thus, transgenic CF mice exhibit decreased clearance of
P. aeruginosa and increased bacterial burdens in the
lung, substantiating a key role for CFTR-mediated bacterial ingestion
in lung clearance of P.
aeruginosa.
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