Reactive-oxygen-species-mediated P. aeruginosa killing is functional in human cystic fibrosis macrophages.

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 in...

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Autores principales: Noemi Cifani, Barbara Pompili, Marco Anile, Miriam Patella, Daniele Diso, Federico Venuta, Giuseppe Cimino, Serena Quattrucci, Enea Gino Di Domenico, Fiorentina Ascenzioni, Paola Del Porto
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Publicado: Public Library of Science (PLoS) 2013
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spelling oai:doaj.org-article:745e9596f2eb4a8095225dec47c04a012021-11-18T08:59:07ZReactive-oxygen-species-mediated P. aeruginosa killing is functional in human cystic fibrosis macrophages.1932-620310.1371/journal.pone.0071717https://doaj.org/article/745e9596f2eb4a8095225dec47c04a012013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23977124/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Pseudomonas 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.Noemi CifaniBarbara PompiliMarco AnileMiriam PatellaDaniele DisoFederico VenutaGiuseppe CiminoSerena QuattrucciEnea Gino Di DomenicoFiorentina AscenzioniPaola Del PortoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 8, p e71717 (2013)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Noemi Cifani
Barbara Pompili
Marco Anile
Miriam Patella
Daniele Diso
Federico Venuta
Giuseppe Cimino
Serena Quattrucci
Enea Gino Di Domenico
Fiorentina Ascenzioni
Paola Del Porto
Reactive-oxygen-species-mediated P. aeruginosa killing is functional in human cystic fibrosis macrophages.
description 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.
format article
author Noemi Cifani
Barbara Pompili
Marco Anile
Miriam Patella
Daniele Diso
Federico Venuta
Giuseppe Cimino
Serena Quattrucci
Enea Gino Di Domenico
Fiorentina Ascenzioni
Paola Del Porto
author_facet Noemi Cifani
Barbara Pompili
Marco Anile
Miriam Patella
Daniele Diso
Federico Venuta
Giuseppe Cimino
Serena Quattrucci
Enea Gino Di Domenico
Fiorentina Ascenzioni
Paola Del Porto
author_sort Noemi Cifani
title Reactive-oxygen-species-mediated P. aeruginosa killing is functional in human cystic fibrosis macrophages.
title_short Reactive-oxygen-species-mediated P. aeruginosa killing is functional in human cystic fibrosis macrophages.
title_full Reactive-oxygen-species-mediated P. aeruginosa killing is functional in human cystic fibrosis macrophages.
title_fullStr Reactive-oxygen-species-mediated P. aeruginosa killing is functional in human cystic fibrosis macrophages.
title_full_unstemmed Reactive-oxygen-species-mediated P. aeruginosa killing is functional in human cystic fibrosis macrophages.
title_sort reactive-oxygen-species-mediated p. aeruginosa killing is functional in human cystic fibrosis macrophages.
publisher Public Library of Science (PLoS)
publishDate 2013
url https://doaj.org/article/745e9596f2eb4a8095225dec47c04a01
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