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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...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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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. |
format | Online Article Text |
id | pubmed-6458182 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
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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