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

Nat Commun. 2019 Apr 10;10(1):1667. doi: 10.1038/s41467-019-09040-0.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Animals
  • Borrelia burgdorferi Group / immunology
  • Brain / cytology
  • Brain / drug effects
  • Brain / immunology
  • Brain / microbiology
  • Cerebrospinal Fluid / cytology*
  • Cerebrospinal Fluid / immunology
  • Cerebrospinal Fluid / microbiology
  • Deoxyribonuclease I / administration & dosage
  • Disease Models, Animal
  • Extracellular Traps / drug effects
  • Extracellular Traps / immunology
  • Extracellular Traps / microbiology*
  • Female
  • Humans
  • Immune Evasion*
  • Lyme Neuroborreliosis / cerebrospinal fluid
  • Lyme Neuroborreliosis / immunology
  • Lyme Neuroborreliosis / microbiology
  • Male
  • Meningitis, Pneumococcal / cerebrospinal fluid
  • Meningitis, Pneumococcal / drug therapy
  • Meningitis, Pneumococcal / immunology*
  • Meningitis, Pneumococcal / microbiology
  • Meningitis, Viral / cerebrospinal fluid
  • Meningitis, Viral / immunology
  • Middle Aged
  • Neutrophils / immunology*
  • Neutrophils / microbiology
  • Rats
  • Rats, Sprague-Dawley
  • Recombinant Proteins / administration & dosage
  • Spinal Puncture
  • Streptococcus pneumoniae / immunology*
  • Streptococcus pneumoniae / isolation & purification
  • Subarachnoid Hemorrhage / cerebrospinal fluid
  • Young Adult

Substances

  • Recombinant Proteins
  • DNASE1 protein, human
  • Deoxyribonuclease I