Division of Infection Medicine, Department of Clinical Sciences, Lund University, 22184, Lund, Sweden.
Center for Translational Neuromedicine, Blegdamsvej 3B, Copenhagen University, 2200, Copenhagen, Denmark.
Nat Commun. 2019 Apr 10;10(1):1667. doi: 10.1038/s41467-019-09040-0.
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.
中性粒细胞是宿主防御的关键介质，在肺炎链球菌引起的急性细菌性脑膜炎中，大量中性粒细胞被招募到中枢神经系统（CNS）。中性粒细胞在感染过程中释放中性粒细胞胞外陷阱（NETs），以捕获和杀死细菌。完整的 NETs 是由去凝聚的 DNA 和中性粒细胞来源的抗菌蛋白组成的纤维状结构。在这里，我们在患有肺炎球菌性脑膜炎的患者的脑脊液（CSF）中观察到 NETs，而在其他形式的脑膜炎中，由于病毒、伯氏疏螺旋体和蛛网膜下腔出血导致 CSF 中中性粒细胞流入，NETs 则不存在。在脑膜炎的大鼠模型中，临床分离株肺炎球菌在 CSF 中诱导 NET 形成。使用 DNAse I 破坏 NETs 可显著降低细菌负荷，表明 NETs 在体内有助于肺炎球菌性脑膜炎的发病机制。我们得出结论，CNS 中的 NETs 降低了细菌清除率，使用 DNAse I 降解 NETs 可能具有重要的治疗意义。
