Proteomics

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Neutrophil extracellular traps in the central nervous system: a novel therapeutic target in pneumococcal meningitis.


ABSTRACT: Neutrophils are crucial mediators of host defense and are recruited to the central nervous system in large numbers during acute bacterial meningitis caused by S. pneumoniae. Neutrophils can release neutrophil extracellular traps (NETs) during infections to trap and kill bacteria. Intact NETs are fibrous structures and mainly consist of decondensed DNA and neutrophil-derived antimicrobial proteins. We report the extensive presence of NETs in the cerebrospinal fluid of patients with pneumococcal meningitis, and absence of NETs in other forms of meningitis caused by viruses, Borrelia and subarachnoid hemorrhage. In a rat model of meningitis, a clinical strain of pneumococci induced NET formation in the cerebrospinal fluid. Importantly, disrupting NETs using DNase I significantly reduced bacterial load, demonstrating that NETs contribute to the pathogenesis of pneumococcal meningitis in vivo. Targeting NETs using DNase may represent a novel indication for an already approved drug as a non-antibiotic therapeutic option to treat acute pneumococcal meningitis.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human) Streptococcus Pneumoniae Tigr4

TISSUE(S): Cerebrospinal Fluid

DISEASE(S): Meningitis

SUBMITTER: Christofer Karlsson  

LAB HEAD: Johan Malmström

PROVIDER: PXD011546 | Pride | 2019-11-12

REPOSITORIES: Pride

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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, an  ...[more]

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