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

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

Author information

1
Division of Infection Medicine, Department of Clinical Sciences, Lund University, 22184, Lund, Sweden. tirthankar.mohanty@med.lu.se.
2
Division of Infection Medicine, Department of Clinical Sciences, Lund University, 22184, Lund, Sweden.
3
Center for Translational Neuromedicine, Blegdamsvej 3B, Copenhagen University, 2200, Copenhagen, Denmark.
4
Department of Experimental Medicine Science, Lund University, Solvegatan 19, 22184, Lund, Sweden.
5
Wallenberg Center for Molecular Medicine, Lund University, Solvegatan 19, 22184, Lund, Sweden.
6
Division of Medical Microbiology, Department of Laboratory Medicine, Lund University, 22184, Lund, Sweden.
7
Clinical Microbiology, Labmedicin, Region Skåne, 22184, Lund, Sweden.
8
Division of Anesthesia and Intensive Care, Department of Clinical Sciences, Lund University, 22184, Lund, Sweden.
9
Department of Neurosurgery, Lund University Hospital, 22185, Lund, Sweden.
10
Department of Anesthesia and Intensive Care, Helsingborg Hospital, 25187, Helsingborg, Sweden.

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.

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