{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T18:35:32Z","timestamp":1791052532641,"version":"4.1.0"},"reference-count":61,"publisher":"National Academy of Sciences","issue":"16","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2000,8]]},"abstract":"<jats:p>\n                    Chronic\n                    <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n                    infection occurs in\n 75\u201390% of patients with cystic fibrosis (CF). It is the foremost\n factor in pulmonary function decline and early mortality. A connection\n has been made between mutant or missing CF transmembrane conductance\n regulator (CFTR) in lung epithelial cell membranes and a failure in\n innate immunity leading to initiation of\n                    <jats:italic>P. aeruginosa<\/jats:italic>\n                    infection. Epithelial cells use CFTR as a receptor for internalization\n of\n                    <jats:italic>P. aeruginosa<\/jats:italic>\n                    via endocytosis and subsequent removal\n of bacteria from the airway. In the absence of functional CFTR, this\n interaction does not occur, allowing for increased bacterial loads in\n the lungs. Binding occurs between the outer core of the bacterial\n lipopolysaccharide and amino acids 108\u2013117 in the first predicted\n extracellular domain of CFTR. In experimentally infected mice,\n inhibiting CFTR-mediated endocytosis of\n                    <jats:italic>P. aeruginosa<\/jats:italic>\n                    by\n inclusion in the bacterial inoculum of either free bacterial\n lipopolysaccharide or CFTR peptide 108\u2013117 resulted in increased\n bacterial counts in the lungs. CFTR is also a receptor on\n gastrointestinal epithelial cells for\n                    <jats:italic>Salmonella\n enterica<\/jats:italic>\n                    serovar Typhi, the etiologic agent of typhoid fever.\n There was a significant decrease in translocation of this organism to\n the gastrointestinal submucosa in transgenic mice that are heterozygous\n carriers of a mutant \u0394F508\n                    <jats:italic>CFTR<\/jats:italic>\n                    allele, suggesting\n heterozygous\n                    <jats:italic>CFTR<\/jats:italic>\n                    carriers may have increased resistance\n to typhoid fever. The identification of CFTR as a receptor for\n bacterial pathogens could underlie the biology of CF lung disease and\n be the basis for the heterozygote advantage for carriers of mutant\n alleles of\n                    <jats:italic>CFTR<\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.1073\/pnas.97.16.8822","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:40:52Z","timestamp":1027680052000},"page":"8822-8828","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":113,"title":["Role of the cystic fibrosis transmembrane conductance regulator in innate immunity to\n                    <i>Pseudomonas aeruginosa<\/i>\n                    infections"],"prefix":"10.1073","volume":"97","author":[{"given":"Gerald B.","family":"Pier","sequence":"first","affiliation":[{"name":"Channing Laboratory, Department of Medicine, Brigham and Women's\r Hospital, Harvard Medical School, 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