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

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T1 - Neutrophil extracellular traps in the central nervous system hinder bacterial clearance during pneumococcal meningitis

AU - Mohanty, Tirthankar

AU - Fisher, Jane

AU - Bakochi, Anahita

AU - Neumann, Ariane

AU - Cardoso, José Francisco Pereira

AU - Karlsson, Christofer A Q

AU - Pavan, Chiara

AU - Lundgaard, Iben

AU - Nilson, Bo

AU - Reinstrup, Peter

AU - Bonnevier, Johan

AU - Cederberg, David

AU - Malmström, Johan

AU - Bentzer, Peter

AU - Linder, Adam

PY - 2019/4/10

Y1 - 2019/4/10

N2 - 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.

AB - 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.

U2 - 10.1038/s41467-019-09040-0

DO - 10.1038/s41467-019-09040-0

M3 - Article

VL - 10

SP - 1667

JO - Nature Communications

T2 - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

ER -