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

Research output: Contribution to journalArticle

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 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.

Details

Authors
Organisations
External organisations
  • University of Copenhagen
  • Regional Laboratories Region Skåne
  • Skåne University Hospital
  • Helsingborg Hospital
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Infectious Medicine
  • Neurosciences
Original languageEnglish
Pages (from-to)1667
JournalNature Communications
Volume10
Issue number1
Publication statusPublished - 2019 Apr 10
Publication categoryResearch
Peer-reviewedYes