title: Reactive-oxygen-species-mediated P. aeruginosa killing is functional in human cystic fibrosis macrophages.
abstract: Pseudomonas aeruginosa is the most common pathogen for chronic lung infection in cystic fibrosis (CF) patients. About 80% of adult CF patients have chronic P. aeruginosa infection, which accounts for much of the morbidity and most of the mortality. Both bacterial genetic adaptations and defective innate immune responses contribute to the bacteria persistence. It is well accepted that CF transmembrane conductance regulator (CFTR) dysfunction impairs the airways-epithelium-mediated lung defence; however, other innate immune cells also appear to be affected, such as neutrophils and macrophages, which thus contribute to this infectious pathology in the CF lung. In macrophages, the absence of CFTR has been linked to defective P. aeruginosa killing, increased pro-inflammatory cytokine secretion, and reduced reactive oxygen species (ROS) production. To learn more about macrophage dysfunction in CF patients, we investigated the generation of the oxidative burst and its impact on bacterial killing in CF macrophages isolated from peripheral blood or lung parenchyma of CF patients, after P. aeruginosa infection. Our data demonstrate that CF macrophages show an oxidative response of similar intensity to that of non-CF macrophages. Intracellular ROS are recognized as one of the earliest microbicidal mechanisms against engulfed pathogens that are activated by macrophages. Accordingly, NADPH inhibition resulted in a significant increase in the intracellular bacteria survival in CF and non-CF macrophages, both as monocyte-derived macrophages and as lung macrophages. These data strongly suggest that the contribution of ROS to P. aeruginosa killing is not affected by CFTR mutations.
authors: Department of Biology and Biotechnology "Charles Darwin" Sapienza University, Rome, Italy.
authors: Noemi
authors: N
authors: Cifani
authors: Barbara
authors: B
authors: Pompili
authors: Marco
authors: M
authors: Anile
authors: Miriam
authors: M
authors: Patella
authors: Daniele
authors: D
authors: Diso
authors: Federico
authors: F
authors: Venuta
authors: Giuseppe
authors: G
authors: Cimino
authors: Serena
authors: S
authors: Quattrucci
authors: Enea Gino
authors: EG
authors: Di Domenico
authors: Fiorentina
authors: F
authors: Ascenzioni
authors: Paola
authors: P
authors: Del Porto
mesh_terms: D000293:Adolescent; D000328:Adult; D002469:Cell Separation; D003550:Cystic Fibrosis / Q000382:microbiology* / Q000473:pathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D042541:Intracellular Space / Q000382:microbiology; D008168:Lung / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology / Q000382:microbiology* / Q000473:pathology*; D008297:Male; D050296:Microbial Viability / Q000187:drug effects; D008875:Middle Aged; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000378:metabolism; D010641:Phenotype; D011552:Pseudomonas Infections / Q000473:pathology; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D016897:Respiratory Burst / Q000187:drug effects; D055815:Young Adult
chemical_list: D004791:Enzyme Inhibitors; D017382:Reactive Oxygen Species; D052247:Nitric Oxide Synthase Type II; D019255:NADPH Oxidases
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