CFTR-dependent susceptibility of the cystic fibrosis-host to Pseudomonas aeruginosa

Abstract

Cystic fibrosis is the most common autosomal recessive disorder in western countries. The disease is characterized by recurrent and chronic infections of the lung in particular with Pseudomonas aeruginosa, Staphylococcus aureus, Burkholderia cepacia, and Haemophilus influenzae. Albeit intensive research in the last years, the molecular mechanisms causing the high susceptibility of cystic fibrosis patients to bacterial infections are still unknown. Animal models provided important novel information on the pathophysiology of cystic fibrosis and mimicked many of the pathological findings in humans, for instance chronic inflammation and increased infection susceptibility. These animal models were recently employed to identify several proteins and lipids that are critically involved in the pathophysiology of cystic fibrosis. Thus, several studies identified death receptors, caveolin proteins, membrane rafts, and alterations of the ceramide metabolism with an accumulation of ceramide in cystic fibrosis lungs to be critically involved in the infection susceptibility, the chronic inflammation, and the reduced mucociliary clearance in cystic fibrosis.