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process is probably initiated in the epithelial cell when it comes into contact with bacteria, and further cellular activation, cytokine secretion, and inflammation may also contribute to elimination of pathogens from infected mucosa. Moreover, not all mutations in CFTR lead to a loss of membrane protein, and defects in CFTR genes that result in a membrane protein that is nonfunctional with regard to chloride ion secretion may also diminish the protein's ability to orchestrate the full epithelial cell response needed to remove P. aeruginosa from the tissue. The identification of CFTR as a protein that binds P. aeruginosa and coordinates the epithelial cell response leading to bacterial clearance indicates a direct connection between mutant CFTR genes and the clinical course of CF. Thus, in addition to its functions as a chloride ion channel, a regulator of sodium, and perhaps a regulator of other ion channels, CFTR is also a key component in innate immunity on mucosal surfaces, serving as a receptor to ingest and clear microbes and contribute to host resistance to infection.

I thank the following individuals from the Channing Laboratory who carried out the work described in this report: Alev Gerceker, Martha Grout, Kazue Hatano, Jeffrey Lyczak, Gloria Meluleni, and Tanweer Zaidi. Work described in this paper was carried out, in part, under National Institutes of Health Grants AI22535, AI22806, and HL58398 and under a Brigham and Women's Hospital Interdisciplinary Seed Grant.

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