Abnormalities in the pulmonary innate immune system in cystic fibrosis.
Pulmonary infection is the dominant clinical feature of cystic fibrosis (CF), but the basis for this susceptibility remains incompletely understood. One hypothesis is that CF airway surface liquid (ASL) is abnormal and interferes with neutrophil function. To study this possibility, we developed an in vitro system in which we collected ASL from primary cultures of normal and CF airway epithelial cells. Microbial killing was less efficient when bacteria were incubated with neutrophils in the presence of ASL from CF epithelia compared with normal ASL. Antimicrobial functions of human neutrophils were assessed in ASL from CF and normal epithelia using a combination of quantitative bacterial culture, flow cytometry, and microfluorescence imaging. The results of these assays of neutrophil function were indistinguishable in CF and normal ASL. In contrast, the direct bactericidal activity of ASL to Escherichia coli and to clinical isolates of Staphylococcus aureus and Pseudomonas aeruginosa was substantially less in CF than in normal ASL, even when highly diluted in media of identical ionic strength. Together, these observations indicate that the antimicrobial properties of ASL in CF are compromised in a manner independent of ionic strength of the ASL, and that this effect is not mediated through a direct effect of the ASL on phagocyte function.
Moraes
Theo J
TJ
Division of Respirology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
Plumb
Jonathan
J
Martin
Raiza
R
Vachon
Eric
E
Cherepanov
Vera
V
Koh
Adeline
A
Loeve
Carola
C
Jongstra-Bilen
Jenny
J
Zurawska
Joanna H
JH
Kus
Julianne V
JV
Burrows
Lori L
LL
Grinstein
Sergio
S
Downey
Gregory P
GP
D001980:Bronchi / Q000166:cytology; D002478:Cells, Cultured; D003550:Cystic Fibrosis / Q000276:immunology* / Q000382:microbiology; D004847:Epithelial Cells / Q000276:immunology* / Q000382:microbiology; D004926:Escherichia coli / Q000254:growth & development; D005089:Exocytosis; D006801:Humans; D007113:Immunity, Innate; D050296:Microbial Viability; D009504:Neutrophils / Q000276:immunology*; D009994:Osmolar Concentration; D010587:Phagocytosis; D011550:Pseudomonas aeruginosa / Q000254:growth & development / Q000302:isolation & purification; D016897:Respiratory Burst; D020545:Respiratory Mucosa / Q000276:immunology* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000254:growth & development / Q000302:isolation & purification