Cellular responses of A549 alveolar epithelial cells to serially collected Pseudomonas aeruginosa from cystic fibrosis patients at different stages of pulmonary infection.
Pseudomonas aeruginosa is the major cause of chronic pulmonary disease in cystic fibrosis (CF) patients. During chronic infection, P. aeruginosa lose certain virulence factors, transform into a mucoid phenotype, and develop antibiotic resistance. We hypothesized that these genetic and phenotypic alterations of P. aeruginosa affect the airway epithelial responses. A549 cells were infected with 27 well-characterized isolates of P. aeruginosa from CF patients obtained during longitudinal observation, or with P. aeruginosa mutant strains lacking flagella, pili, lipopolysaccharide, or pyocyanin. Pseudomonas aeruginosa isolates from the early stages of the infection exhibited high adherence to A549 cells, were readily internalized, and able to induce reactive oxygen species (ROS) production, apoptosis of infected cells, and the release of granulocyte macrophage colony-stimulating factor. Late P. aeruginosa isolates collected from patients with chronic lung infection were shown to have reduced adherence to and internalization into A549 cells compared with bacteria from patients with intermittent P. aeruginosa colonization, and induced lower production of ROS and apoptosis, but caused high proinflammatory cytokine and adhesion molecule expression. Our findings suggest that despite the loss of virulence factors during the adaptation process in the CF lung by late P. aeruginosa strains, they retain high proinflammatory abilities that likely contribute to the disease pathogenesis.
Hawdon
Nicole A
NA
Lakehead University, ON, Canada.
Aval
Pouya Sadeghi
PS
Barnes
Rebecca J
RJ
Gravelle
Sean K
SK
Rosengren
Jessica
J
Khan
Sarah
S
Ciofu
Oana
O
Johansen
Helle Krogh
HK
Høiby
Niels
N
Ulanova
Marina
M
D017209:Apoptosis; D001422:Bacterial Adhesion; D002460:Cell Line; D003550:Cystic Fibrosis / Q000150:complications*; D016207:Cytokines / Q000378:metabolism; D004847:Epithelial Cells / Q000276:immunology / Q000382:microbiology*; D006801:Humans; D011552:Pseudomonas Infections / Q000382:microbiology*; D011550:Pseudomonas aeruginosa / Q000276:immunology / Q000302:isolation & purification / Q000472:pathogenicity*; D017382:Reactive Oxygen Species / Q000378:metabolism
D016207:Cytokines; D017382:Reactive Oxygen Species