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TITLE |
AUTHORS |
KEYWORDS |
MATERIALS & METHODS
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MICROSCOPIC
TECHNIQUES |
SPECIES |
MORPHOLOGY |
CELL
LINE |
| 624 |
Transgenic
Cystic Fibrosis Mice Exhibit Reduced Early
Clearance of Pseudomonas aeruginosa from the Respiratory
Tract |
Torsten
H. Schroeder, Nina Reiniger, Gloria Meluleni, Martha Grout, Fadie T. Coleman, Gerald B. Pier |
cystic
fibrosis, Pseudomonas aeruginosa, CFTR-mediated
bacterial ingestion |
The tracheas were then placed
in F12 medium and transferred into a 35-mm experimental chamber with a glass
bottom (Plastek Cultureware, Ashland, MA).
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confocal
microscopy |
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P.
aeruginosa strain PAO1 |
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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 DF508 Cftr allele or an allele with a Cftr stop codon (S489X). Intranasal application
achieved P. aeruginosa lung infection in inbred C57BL/6 DF508 Cftr mice, whereas DF508 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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