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

Tirthankar Mohanty (), Jane Fisher, Anahita Bakochi, Ariane Neumann, José Francisco Pereira Cardoso, Christofer A. Q. Karlsson, Chiara Pavan, Iben Lundgaard, Bo Nilson, Peter Reinstrup, Johan Bonnevier, David Cederberg, Johan Malmström, Peter Bentzer and Adam Linder
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Tirthankar Mohanty: Lund University
Jane Fisher: Lund University
Anahita Bakochi: Lund University
Ariane Neumann: Lund University
José Francisco Pereira Cardoso: Lund University
Christofer A. Q. Karlsson: Lund University
Chiara Pavan: Copenhagen University
Iben Lundgaard: Lund University
Bo Nilson: Lund University
Peter Reinstrup: Lund University
Johan Bonnevier: Lund University
David Cederberg: Lund University Hospital
Johan Malmström: Lund University
Peter Bentzer: Lund University
Adam Linder: Lund University

Nature Communications, 2019, vol. 10, issue 1, 1-13

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-09040-0

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