Cystic Fibrosis Sputum Impairs the Ability of Neutrophils to Kill

Cystic fibrosis (CF) airway disease is characterized by chronic microbial infections and infiltration of inflammatory polymorphonuclear (PMN) granulocytes. is a major lung pathogen in CF that persists despite the presence of PMNs and has been associated with CF lung function decline. While PMNs represent the main mechanism of the immune system to kill , it remains largely unknown why PMNs fail to eliminate in CF. The goal of this study was to observe how the CF airway environment affects killing by PMNs. PMNs were isolated from the blood of healthy volunteers and CF patients. Clinical isolates of were obtained from the airways of CF patients. The results show that PMNs from healthy volunteers were able to kill all CF isolates and laboratory strains of tested in vitro. The extent of killing varied among strains. When PMNs were pretreated with supernatants of CF sputum, killing was significantly inhibited suggesting that the CF airway environment compromises PMN antibacterial functions. CF blood PMNs were capable of killing . Although bacterial killing was inhibited with CF sputum, PMN binding and phagocytosis of was not diminished. The -induced respiratory burst and neutrophil extracellular trap release from PMNs also remained uninhibited by CF sputum. In summary, our data demonstrate that the CF airway environment limits killing of by PMNs and provides a new in vitro experimental model to study this phenomenon and its mechanism.