Neutrophil extracellular traps in the central nervous system hinder bacterial clearance during pneumococcal meningitis.
Adolescent
Adult
Aged
Animals
Borrelia burgdorferi Group
/ immunology
Brain
/ cytology
Cerebrospinal Fluid
/ cytology
Deoxyribonuclease I
/ administration & dosage
Disease Models, Animal
Extracellular Traps
/ drug effects
Female
Humans
Immune Evasion
Lyme Neuroborreliosis
/ cerebrospinal fluid
Male
Meningitis, Pneumococcal
/ cerebrospinal fluid
Meningitis, Viral
/ cerebrospinal fluid
Middle Aged
Neutrophils
/ immunology
Rats
Rats, Sprague-Dawley
Recombinant Proteins
/ administration & dosage
Spinal Puncture
Streptococcus pneumoniae
/ immunology
Subarachnoid Hemorrhage
/ cerebrospinal fluid
Young Adult
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
10 04 2019
10 04 2019
Historique:
received:
21
03
2018
accepted:
12
02
2019
entrez:
12
4
2019
pubmed:
12
4
2019
medline:
30
4
2019
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 30971685
doi: 10.1038/s41467-019-09040-0
pii: 10.1038/s41467-019-09040-0
pmc: PMC6458182
doi:
Substances chimiques
Recombinant Proteins
0
DNASE1 protein, human
EC 3.1.21.1
Deoxyribonuclease I
EC 3.1.21.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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