Division of Drug Research, Department of Medical and Health Sciences, Linköping University, SE-581 85 Linköping, Sweden.
Division of Neuro and Inflammation Sciences, Department of Clinical and Experimental Medicine, Linköping University, SE-581 85 Linköping, Sweden.
Cells. 2019 Dec 23;9(1):43. doi: 10.3390/cells9010043.
Neutrophils operate as part of the innate defence in the skin and may eliminate the spirochaete via phagocytosis, oxidative bursts, and hydrolytic enzymes. However, their importance in Lyme neuroborreliosis (LNB) is unclear. Neutrophil extracellular trap (NET) formation, which is associated with the production of reactive oxygen species, involves the extrusion of the neutrophil DNA to form traps that incapacitate bacteria and immobilise viruses. Meanwhile, NET formation has recently been studied in pneumococcal meningitis, the role of NETs in other central nervous system (CNS) infections has previously not been studied. Here, cerebrospinal fluid (CSF) samples from clinically well-characterised children ( = 111) and adults ( = 64) with LNB and other CNS infections were analysed for NETs (DNA/myeloperoxidase complexes) and elastase activity. NETs were detected more frequently in the children than the adults ( = 0.01). NET presence was associated with higher CSF levels of CXCL1 ( < 0.001), CXCL6 ( = 0.007), CXCL8 ( = 0.003), CXCL10 ( < 0.001), MMP-9 ( = 0.002), TNF ( = 0.02), IL-6 ( < 0.001), and IL-17A ( = 0.03). NETs were associated with fever ( = 0.002) and correlated with polynuclear pleocytosis (r = 0.53, < 0.0001). We show that neutrophil activation and active NET formation occur in the CSF samples of children and adults with CNS infections, mainly caused by and neurotropic viruses. The role of NETs in the early phase of viral/bacterial CNS infections warrants further investigation.
中性粒细胞作为皮肤固有防御的一部分发挥作用,可通过吞噬作用、氧化爆发和水解酶来消除螺旋体。然而,它们在莱姆神经Borreliosis(LNB)中的重要性尚不清楚。中性粒细胞胞外陷阱(NET)的形成与活性氧的产生有关,涉及到中性粒细胞 DNA 的挤出,形成陷阱,使细菌失能并使病毒固定。同时,最近在肺炎球菌性脑膜炎中研究了 NET 形成,NET 在其他中枢神经系统(CNS)感染中的作用以前尚未研究过。在这里,对临床特征良好的儿童(= 111)和成人(= 64)的脑脊液(CSF)样本进行了分析,以检测 NET(DNA/髓过氧化物酶复合物)和弹性蛋白酶活性。儿童中 NET 的检出率高于成人(= 0.01)。NET 的存在与 CSF 中更高水平的 CXCL1(<0.001)、CXCL6(= 0.007)、CXCL8(= 0.003)、CXCL10(<0.001)、MMP-9(= 0.002)、TNF(= 0.02)、IL-6(<0.001)和 IL-17A(= 0.03)相关。NET 与发热(= 0.002)相关,并与多核白细胞增多症相关(r = 0.53,<0.0001)。我们表明,中性粒细胞的活化和活跃的 NET 形成发生在患有 CNS 感染的儿童和成人的 CSF 样本中,这些感染主要由 引起,并伴有神经嗜性病毒。NET 在病毒/细菌中枢神经系统感染的早期阶段的作用需要进一步研究。