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

Mohanty, Tirthankar LU ; Fisher, Jane LU ; Bakochi, Anahita LU ; Neumann, Ariane LU ; Cardoso, José Francisco Pereira LU ; Karlsson, Christofer A Q LU ; Pavan, Chiara LU ; Lundgaard, Iben LU ; Nilson, Bo LU and Reinstrup, Peter LU , et al. (2019) In Nature Communications 10(1). p.1667-1667
Abstract

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... (More)

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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Nature Communications
volume
10
issue
1
pages
1667 - 1667
publisher
Nature Publishing Group
external identifiers
  • scopus:85064251732
ISSN
2041-1723
DOI
10.1038/s41467-019-09040-0
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English
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yes
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ccb57110-a672-44e8-8dc6-ae25c0e8875b
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2019-04-17 09:13:03
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2019-07-14 04:51:09
@article{ccb57110-a672-44e8-8dc6-ae25c0e8875b,
  abstract     = {<p>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.</p>},
  author       = {Mohanty, Tirthankar and Fisher, Jane and Bakochi, Anahita and Neumann, Ariane and Cardoso, José Francisco Pereira and Karlsson, Christofer A Q and Pavan, Chiara and Lundgaard, Iben and Nilson, Bo and Reinstrup, Peter and Bonnevier, Johan and Cederberg, David and Malmström, Johan and Bentzer, Peter and Linder, Adam},
  issn         = {2041-1723},
  language     = {eng},
  month        = {04},
  number       = {1},
  pages        = {1667--1667},
  publisher    = {Nature Publishing Group},
  series       = {Nature Communications},
  title        = {Neutrophil extracellular traps in the central nervous system hinder bacterial clearance during pneumococcal meningitis},
  url          = {http://dx.doi.org/10.1038/s41467-019-09040-0},
  volume       = {10},
  year         = {2019},
}