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Neutrophil extracellular traps in the central nervous system hinder bacterial clearance during pneumococcal meningitis

Neutrophils are crucial mediators of host defense that are recruited to the central nervous system (CNS) in large numbers during acute bacterial meningitis caused by Streptococcus pneumoniae. Neutrophils release neutrophil extracellular traps (NETs) during infections to trap and kill bacteria. Intac...

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Autores principales: Mohanty, Tirthankar, Fisher, Jane, Bakochi, Anahita, Neumann, Ariane, Cardoso, José Francisco Pereira, Karlsson, Christofer A. Q., Pavan, Chiara, Lundgaard, Iben, Nilson, Bo, Reinstrup, Peter, Bonnevier, Johan, Cederberg, David, Malmström, Johan, Bentzer, Peter, Linder, Adam
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6458182/
https://www.ncbi.nlm.nih.gov/pubmed/30971685
http://dx.doi.org/10.1038/s41467-019-09040-0
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author Mohanty, Tirthankar
Fisher, Jane
Bakochi, Anahita
Neumann, Ariane
Cardoso, José Francisco Pereira
Karlsson, Christofer A. Q.
Pavan, Chiara
Lundgaard, Iben
Nilson, Bo
Reinstrup, Peter
Bonnevier, Johan
Cederberg, David
Malmström, Johan
Bentzer, Peter
Linder, Adam
author_facet Mohanty, Tirthankar
Fisher, Jane
Bakochi, Anahita
Neumann, Ariane
Cardoso, José Francisco Pereira
Karlsson, Christofer A. Q.
Pavan, Chiara
Lundgaard, Iben
Nilson, Bo
Reinstrup, Peter
Bonnevier, Johan
Cederberg, David
Malmström, Johan
Bentzer, Peter
Linder, Adam
author_sort Mohanty, Tirthankar
collection PubMed
description Neutrophils are crucial mediators of host defense that are recruited to the central nervous system (CNS) in large numbers during acute bacterial meningitis caused by Streptococcus pneumoniae. Neutrophils release neutrophil extracellular traps (NETs) during infections to trap and kill bacteria. Intact NETs are fibrous structures composed of decondensed DNA and neutrophil-derived antimicrobial proteins. Here we show NETs in the cerebrospinal fluid (CSF) of patients with pneumococcal meningitis, and their absence in other forms of meningitis with neutrophil influx into the CSF caused by viruses, Borrelia and subarachnoid hemorrhage. In a rat model of meningitis, a clinical strain of pneumococci induced NET formation in the CSF. Disrupting NETs using DNase I significantly reduces bacterial load, demonstrating that NETs contribute to pneumococcal meningitis pathogenesis in vivo. We conclude that NETs in the CNS reduce bacterial clearance and degrading NETs using DNase I may have significant therapeutic implications.
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spelling pubmed-64581822019-04-12 Neutrophil extracellular traps in the central nervous system hinder bacterial clearance during pneumococcal meningitis Mohanty, Tirthankar Fisher, Jane Bakochi, Anahita Neumann, Ariane Cardoso, José Francisco Pereira Karlsson, Christofer A. Q. Pavan, Chiara Lundgaard, Iben Nilson, Bo Reinstrup, Peter Bonnevier, Johan Cederberg, David Malmström, Johan Bentzer, Peter Linder, Adam Nat Commun Article Neutrophils are crucial mediators of host defense that are recruited to the central nervous system (CNS) in large numbers during acute bacterial meningitis caused by Streptococcus pneumoniae. Neutrophils release neutrophil extracellular traps (NETs) during infections to trap and kill bacteria. Intact NETs are fibrous structures composed of decondensed DNA and neutrophil-derived antimicrobial proteins. Here we show NETs in the cerebrospinal fluid (CSF) of patients with pneumococcal meningitis, and their absence in other forms of meningitis with neutrophil influx into the CSF caused by viruses, Borrelia and subarachnoid hemorrhage. In a rat model of meningitis, a clinical strain of pneumococci induced NET formation in the CSF. Disrupting NETs using DNase I significantly reduces bacterial load, demonstrating that NETs contribute to pneumococcal meningitis pathogenesis in vivo. We conclude that NETs in the CNS reduce bacterial clearance and degrading NETs using DNase I may have significant therapeutic implications. Nature Publishing Group UK 2019-04-10 /pmc/articles/PMC6458182/ /pubmed/30971685 http://dx.doi.org/10.1038/s41467-019-09040-0 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Mohanty, Tirthankar
Fisher, Jane
Bakochi, Anahita
Neumann, Ariane
Cardoso, José Francisco Pereira
Karlsson, Christofer A. Q.
Pavan, Chiara
Lundgaard, Iben
Nilson, Bo
Reinstrup, Peter
Bonnevier, Johan
Cederberg, David
Malmström, Johan
Bentzer, Peter
Linder, Adam
Neutrophil extracellular traps in the central nervous system hinder bacterial clearance during pneumococcal meningitis
title Neutrophil extracellular traps in the central nervous system hinder bacterial clearance during pneumococcal meningitis
title_full Neutrophil extracellular traps in the central nervous system hinder bacterial clearance during pneumococcal meningitis
title_fullStr Neutrophil extracellular traps in the central nervous system hinder bacterial clearance during pneumococcal meningitis
title_full_unstemmed Neutrophil extracellular traps in the central nervous system hinder bacterial clearance during pneumococcal meningitis
title_short Neutrophil extracellular traps in the central nervous system hinder bacterial clearance during pneumococcal meningitis
title_sort neutrophil extracellular traps in the central nervous system hinder bacterial clearance during pneumococcal meningitis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6458182/
https://www.ncbi.nlm.nih.gov/pubmed/30971685
http://dx.doi.org/10.1038/s41467-019-09040-0
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