Neutrophil extracellular traps in the central nervous system hinder bacterial clearance during pneumococcal meningitis
Neutrophil extracellular traps in the central nervous system hinder bacterial clearance during pneumococcal meningitis
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DOI：
10.1038/s41467-019-09040-0
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发表时间：
2019-04-10
影响因子：
16.6
通讯作者：
Linder, Adam
中科院分区：
文献类型：
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作者：
Mohanty, Tirthankar;Fisher, Jane;Linder, Adam
中性粒细胞是宿主防御的重要介质，在肺炎链球菌引起的急性细菌性脑膜炎期间，中性粒细胞被大量招募到中枢神经系统（CNS）。中性粒细胞在感染期间释放中性粒细胞胞外陷阱（NETs）来捕获和杀死细菌。完整的net是由去致密DNA和中性粒细胞衍生的抗菌蛋白组成的纤维结构。本文显示肺炎球菌脑膜炎患者脑脊液（CSF）中存在NETs，而其他形式的脑膜炎（由病毒、疏螺旋体和蛛网膜下腔出血引起的中性粒细胞流入脑脊液）中没有NETs。在大鼠脑膜炎模型中，一种肺炎球菌临床菌株诱导脑脊液中NET的形成。使用DNase I破坏NETs可显著减少细菌负荷，证明NETs有助于体内肺炎球菌脑膜炎的发病机制。我们的结论是，中枢神经系统中的NETs减少细菌清除率，使用DNase I降解NETs可能具有重要的治疗意义。
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.