Absence of the cystic fibrosis transmembrane regulator (Cftr) from myeloid-derived cells slows resolution of inflammation and infection

• Published in: Journal of leukocyte biology Vol. 92; no. 5; pp. 1111 - 1122
• Main Authors: Bonfield, T. L., Hodges, C. A., Cotton, C. U., Drumm, M. L.
• Format: Journal Article
• Language: English
• Published: United States Society for Leukocyte Biology 01.11.2012
• Subjects: Animals; Cystic Fibrosis - genetics; Cystic Fibrosis - immunology; Cystic Fibrosis - physiopathology; Cystic Fibrosis Transmembrane Conductance Regulator - deficiency; Cystic Fibrosis Transmembrane Conductance Regulator - genetics; Cystic Fibrosis Transmembrane Conductance Regulator - immunology; Disease Models, Animal; Host Defense & Pathophysiology; immunity; Inflammation - immunology; lysozyme‐M; Mice; Mice, Inbred C57BL; murine knockout model; Myeloid Cells - immunology; potential difference; Pseudomonas aeruginosa; Pseudomonas Infections - immunology; Respiratory Tract Infections - immunology
• ISSN: 0741-5400; 1938-3673
• DOI: 10.1189/jlb.0412188

Cftr is directly involved in myeloid cell function, contributing to the pathophysiological phenotype of the CF lung. The absence or reduction of CFTR function causes CF and results in a pulmonary milieu characterized by bacterial colonization and unresolved inflammation. The ineffectiveness at controlling infection by species such as Pseudomonas aeruginosa suggests defects in innate immunity. Macrophages, neutrophils, and DCs have all been shown to express CFTR mRNA but at low levels, raising the question of whether CFTR has a functional role in these cells. Bone marrow transplants between CF and non‐CF mice suggest that these cells are inherently different; we confirm this observation using conditional inactivation of Cftr in myeloid‐derived cells. Mice lacking Cftr in myeloid cells overtly appear indistinguishable from non‐CF mice until challenged with bacteria instilled into the lungs and airways, at which point, they display survival and inflammatory profiles intermediate in severity as compared with CF mice. These studies demonstrate that Cftr is involved directly in myeloid cell function and imply that these cells contribute to the pathophysiological phenotype of the CF lung.