Neutrophil primary granule exocytosis in early cystic fibrosis airways is triggered by specific microbes

Neutrophils in cystic fibrosis (CF) lungs are reprogrammed into a granule-releasing phenotype associated with proteolytic airway damage. Triggers of this process are unknown; however, an infection may be implicated. This thesis developed laboratory models to assess the responses of human airway cells and neutrophils to microbes. Both pathogenic and resident airway bacteria in the lungs of children with CF induced changes in the airway epithelial microenvironment that activated neutrophil granule exocytosis. Pseudomonas aeruginosa and Prevotella nigrescens were specifically observed to elicit this phenotype. Future work aims to characterise reprogramming mechanisms and identify targeted therapeutics to prevent neutrophil-driven CF lung damage.