Abstract
Cystic Fibrosis Transmembrane Regulator (CFTR) dysfunction is associated with epithelial cell vulnerability and with dysregulation of the local inflammatory responses resulting in excessive airway neutrophilic inflammation and pathogen growth. In combination with impaired mucociliary clearance, and dysregulation of defense function, bacterial infection follows with eventual airway damage and remodeling. Because of these inherent vulnerabilities, viral infections are also more severe and prolonged and appear to render the airway even more prone to bacterial infection. Airway acidity, deficient nitric oxide production and increased iron concentrations, further enhance the airway milieu's susceptibility to infection. Novel diagnostic techniques of the airway microbiome elucidate the coexistence of an array of non-virulent taxa beyond the recognized virulent organisms, predominantly Pseudomonas aeruginosa. The complex interplay between these two bacterial populations, including upregulation of virulence genes and utilization of mucin as a nutrient source, modulates the action of pathogens, modifies the CF airway milieu and contributes to the processes leading to airway derangement. The review provides an update on recent advances of the complex mechanisms that render the CF airway vulnerable to inflammation, infection and ultimately structural damage, the key pathogenetic elements of CF. The recent contributions on CF pathogenesis will hopefully help in identifying new prophylactic measures and therapeutic targets for this highly destructive disorder.
