Scavenging of reactive oxygen species by tryptophan metabolites helps Pseudomonas aeruginosa escape neutrophil killing

Details

Serval ID
serval:BIB_0A6007EAF708
Type
Article: article from journal or magazin.
Collection
Publications
Title
Scavenging of reactive oxygen species by tryptophan metabolites helps Pseudomonas aeruginosa escape neutrophil killing
Journal
Free Radic Biol Med
Author(s)
Genestet C., Le Gouellec A., Chaker H., Polack B., Guery B., Toussaint B., Stasia M. J.
ISSN
1873-4596 (Electronic)
ISSN-L
0891-5849
Publication state
Published
Issued date
08/2014
Volume
73
Pages
400-10
Language
english
Notes
Genestet, Charlotte
Le Gouellec, Audrey
Chaker, Hichem
Polack, Benoit
Guery, Benoit
Toussaint, Bertrand
Stasia, Marie Jose
eng
Research Support, Non-U.S. Gov't
Review
Free Radic Biol Med. 2014 Aug;73:400-10. doi: 10.1016/j.freeradbiomed.2014.06.003. Epub 2014 Jun 12.
Abstract
Pseudomonas aeruginosa is responsible for persistent infections in cystic fibrosis patients, suggesting an ability to circumvent innate immune defenses. This bacterium uses the kynurenine pathway to catabolize tryptophan. Interestingly, many host cells also produce kynurenine, which is known to control immune system homeostasis. We showed that most strains of P. aeruginosa isolated from cystic fibrosis patients produce a high level of kynurenine. Moreover, a strong transcriptional activation of kynA (the first gene involved in the kynurenine pathway) was observed upon contact with immune cells and particularly with neutrophils. In addition, using coculture of human neutrophils with various strains of P. aeruginosa producing no (DeltakynA) or a high level of kynurenine (DeltakynU or DeltakynA pkynA), we demonstrated that kynurenine promotes bacterial survival. In addition, increasing the amount kynurenine inhibits reactive oxygen species production by activated neutrophils, as evaluated by chemiluminescence with luminol or isoluminol or SOD-sensitive cytochrome c reduction assay. This inhibition is due neither to a phagocytosis defect nor to direct NADPH oxidase inhibition. Indeed, kynurenine has no effect on oxygen consumption by neutrophils activated by PMA or opsonized zymosan. Using in vitro reactive oxygen species-producing systems, we showed that kynurenine scavenges hydrogen peroxide and, to a lesser extent, superoxide. Kynurenines scavenging effect occurs mainly intracellularly after bacterial stimulation, probably in the phagosome. In conclusion, the kynurenine pathway allows P. aeruginosa to circumvent the innate immune response by scavenging neutrophil reactive oxygen species production.
Keywords
Cystic Fibrosis/immunology/microbiology, Free Radical Scavengers/metabolism, Humans, Hydrogen Peroxide/metabolism, Hydrolases/genetics, Immune Evasion, Kynurenic Acid/metabolism, Kynurenine/biosynthesis/genetics/*metabolism, Neutrophils/*immunology, Oxygen Consumption, Pseudomonas Infections/immunology, Pseudomonas aeruginosa/*immunology/*metabolism/pathogenicity, Reactive Oxygen Species/*metabolism, Tryptophan/metabolism, Free radicals, Kynurenine, Neutrophils, P. aeruginosa, Reactive oxygen species, Resistance, Scavenger, Tryptophan metabolites
Pubmed
Create date
29/04/2021 10:59
Last modification date
30/04/2021 6:38
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