Neutrophil extracellular trap formation in the Streptococcus suis-infected cerebrospinal fluid compartment
Neutrophil extracellular trap formation in the Streptococcus suis-infected cerebrospinal fluid compartment
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DOI：
10.1111/cmi.12649
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发表时间：
2017-02-01
影响因子：
3.4
通讯作者：
von Koeckritz-Blickwede, Maren
中科院分区：
文献类型：
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作者：
de Buhr, Nicole;Reuner, Friederike;von Koeckritz-Blickwede, Maren
猪链球菌是引起猪和人类脑膜炎的重要病原体。神经元胞外陷阱（NETs）被认为是宿主抵抗不同病原体的防御机制。在此，尽管存在活性核酸酶，但在猪链球菌感染仔猪的脑脊液（CSF）中检测到NET。为了研究猪链球菌和嗜中性粒细胞通过脉络丛上皮细胞屏障迁移后的NET形成和NET降解，使用了先前描述的人血-CSF屏障模型。尽管存在活性核酸酶，但在CSF隔室中记录了NET和相应的链球菌截留。猪链球菌野生型和不同的猪链球菌核酸酶突变体的比较分析没有揭示NET形成或细菌存活的显著差异。有趣的是，转录表达的人cathelicidin LL-37，NET稳定因子，增加后，中性粒细胞通过脉络丛上皮细胞屏障的迁移。与此一致，猪组织蛋白酶抑制剂PR-39在患有脑膜炎的仔猪的CSF中显著增加。此外，我们证实PR-39与感染CSF中的NET相关，并抑制细菌核酸酶对中性粒细胞DNA的降解。总之，中性粒细胞在突破感染的脉络丛上皮后形成NETs，并且这些NETs可能受到抗细菌核酸酶的抗菌肽的保护。
Streptococcus suis is an important meningitis-causing pathogen in pigs and humans. Neutrophil extracellular traps (NETs) have been identified as host defense mechanism against different pathogens. Here, NETs were detected in the cerebrospinal fluid (CSF) of S.suis-infected piglets despite the presence of active nucleases. To study NET-formation and NET-degradation after transmigration of S.suis and neutrophils through the choroid plexus epithelial cell barrier, a previously described model of the human blood-CSF barrier was used. NETs and respective entrapment of streptococci were recorded in the CSF compartment" despite the presence of active nucleases. Comparative analysis of S.suis wildtype and different S.suis nuclease mutants did not reveal significant differences in NET-formation or bacterial survival. Interestingly, transcript expression of the human cathelicidin LL-37, a NET-stabilizing factor, increased after transmigration of neutrophils through the choroid plexus epithelial cell barrier. In good accordance, the porcine cathelicidin PR-39 was significantly increased in CSF of piglets with meningitis. Furthermore, we confirmed that PR-39 is associated with NETs in infected CSF and inhibits neutrophil DNA degradation by bacterial nucleases. In conclusion, neutrophils form NETs after breaching the infected choroid plexus epithelium, and those NETs may be protected by antimicrobial peptides against bacterial nucleases.