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Regulation of Pseudomonas aeruginosa-Mediated Neutrophil Extracellular Traps

Pseudomonas aeruginosa is the most prevalent opportunistic pathogen in the airways of cystic fibrosis (CF) patients. The pulmonary disorder is characterized by recurrent microbial infections and an exaggerated host inflammatory immune response led primarily by influx of neutrophils. Under these cond...

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Autores principales: Skopelja-Gardner, Sladjana, Theprungsirikul, Jomkuan, Lewis, Kimberley A., Hammond, John H., Carlson, Kyrsten M., Hazlett, Haley F., Nymon, Amanda, Nguyen, Dao, Berwin, Brent L., Hogan, Deborah A., Rigby, William F. C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6657737/
https://www.ncbi.nlm.nih.gov/pubmed/31379861
http://dx.doi.org/10.3389/fimmu.2019.01670
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author Skopelja-Gardner, Sladjana
Theprungsirikul, Jomkuan
Lewis, Kimberley A.
Hammond, John H.
Carlson, Kyrsten M.
Hazlett, Haley F.
Nymon, Amanda
Nguyen, Dao
Berwin, Brent L.
Hogan, Deborah A.
Rigby, William F. C.
author_facet Skopelja-Gardner, Sladjana
Theprungsirikul, Jomkuan
Lewis, Kimberley A.
Hammond, John H.
Carlson, Kyrsten M.
Hazlett, Haley F.
Nymon, Amanda
Nguyen, Dao
Berwin, Brent L.
Hogan, Deborah A.
Rigby, William F. C.
author_sort Skopelja-Gardner, Sladjana
collection PubMed
description Pseudomonas aeruginosa is the most prevalent opportunistic pathogen in the airways of cystic fibrosis (CF) patients. The pulmonary disorder is characterized by recurrent microbial infections and an exaggerated host inflammatory immune response led primarily by influx of neutrophils. Under these conditions, chronic colonization with P. aeruginosa is associated with diminished pulmonary function and increased morbidity and mortality. P. aeruginosa has a wide array of genetic mechanisms that facilitate its persistent colonization of the airway despite extensive innate host immune responses. Loss of function mutations in the quorum sensing regulatory gene lasR have been shown to confer survival advantage and a more pathogenic character to P. aeruginosa in CF patients. However, the strategies used by LasR-deficient P. aeruginosa to modulate neutrophil-mediated bactericidal functions are unknown. We sought to understand the role of LasR in P. aeruginosa-mediated neutrophil extracellular trap (NET) formation, an important anti-microbial mechanism deployed by neutrophils, the first-line responder in the infected airway. We observe mechanistic and phenotypic differences between NETs triggered by LasR-sufficient and LasR-deficient P. aeruginosa strains. We uncover that LasR-deficient P. aeruginosa strains fail to induce robust NET formation in both human and murine neutrophils, independently of bacterial motility or LPS expression. LasR does not mediate NET release via downstream quorum sensing signaling pathways but rather via transcriptional regulation of virulence factors, including, but not restricted to, LasB elastase and LasA protease. Finally, our studies uncover the differential requirements for NADPH oxidase in NET formation triggered by different P. aeruginosa strains.
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spelling pubmed-66577372019-08-02 Regulation of Pseudomonas aeruginosa-Mediated Neutrophil Extracellular Traps Skopelja-Gardner, Sladjana Theprungsirikul, Jomkuan Lewis, Kimberley A. Hammond, John H. Carlson, Kyrsten M. Hazlett, Haley F. Nymon, Amanda Nguyen, Dao Berwin, Brent L. Hogan, Deborah A. Rigby, William F. C. Front Immunol Immunology Pseudomonas aeruginosa is the most prevalent opportunistic pathogen in the airways of cystic fibrosis (CF) patients. The pulmonary disorder is characterized by recurrent microbial infections and an exaggerated host inflammatory immune response led primarily by influx of neutrophils. Under these conditions, chronic colonization with P. aeruginosa is associated with diminished pulmonary function and increased morbidity and mortality. P. aeruginosa has a wide array of genetic mechanisms that facilitate its persistent colonization of the airway despite extensive innate host immune responses. Loss of function mutations in the quorum sensing regulatory gene lasR have been shown to confer survival advantage and a more pathogenic character to P. aeruginosa in CF patients. However, the strategies used by LasR-deficient P. aeruginosa to modulate neutrophil-mediated bactericidal functions are unknown. We sought to understand the role of LasR in P. aeruginosa-mediated neutrophil extracellular trap (NET) formation, an important anti-microbial mechanism deployed by neutrophils, the first-line responder in the infected airway. We observe mechanistic and phenotypic differences between NETs triggered by LasR-sufficient and LasR-deficient P. aeruginosa strains. We uncover that LasR-deficient P. aeruginosa strains fail to induce robust NET formation in both human and murine neutrophils, independently of bacterial motility or LPS expression. LasR does not mediate NET release via downstream quorum sensing signaling pathways but rather via transcriptional regulation of virulence factors, including, but not restricted to, LasB elastase and LasA protease. Finally, our studies uncover the differential requirements for NADPH oxidase in NET formation triggered by different P. aeruginosa strains. Frontiers Media S.A. 2019-07-18 /pmc/articles/PMC6657737/ /pubmed/31379861 http://dx.doi.org/10.3389/fimmu.2019.01670 Text en Copyright © 2019 Skopelja-Gardner, Theprungsirikul, Lewis, Hammond, Carlson, Hazlett, Nymon, Nguyen, Berwin, Hogan and Rigby. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Skopelja-Gardner, Sladjana
Theprungsirikul, Jomkuan
Lewis, Kimberley A.
Hammond, John H.
Carlson, Kyrsten M.
Hazlett, Haley F.
Nymon, Amanda
Nguyen, Dao
Berwin, Brent L.
Hogan, Deborah A.
Rigby, William F. C.
Regulation of Pseudomonas aeruginosa-Mediated Neutrophil Extracellular Traps
title Regulation of Pseudomonas aeruginosa-Mediated Neutrophil Extracellular Traps
title_full Regulation of Pseudomonas aeruginosa-Mediated Neutrophil Extracellular Traps
title_fullStr Regulation of Pseudomonas aeruginosa-Mediated Neutrophil Extracellular Traps
title_full_unstemmed Regulation of Pseudomonas aeruginosa-Mediated Neutrophil Extracellular Traps
title_short Regulation of Pseudomonas aeruginosa-Mediated Neutrophil Extracellular Traps
title_sort regulation of pseudomonas aeruginosa-mediated neutrophil extracellular traps
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6657737/
https://www.ncbi.nlm.nih.gov/pubmed/31379861
http://dx.doi.org/10.3389/fimmu.2019.01670
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