In vitro resistance mechanisms of Neisseria meningitidis against neutrophil extracellular traps
In vitro resistance mechanisms of Neisseria meningitidis against neutrophil extracellular traps
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DOI：
10.1111/mmi.12288
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发表时间：
2013-08-01
影响因子：
3.6
通讯作者：
Vogel, Ulrich
中科院分区：
文献类型：
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作者：
Lappann, Martin;Danhof, Sophia;Vogel, Ulrich
脑膜炎奈瑟菌（Nm）是儿童败血症的主要原因。Nm败血症在非常快速的疾病进展、高的体内细菌复制率及其相当大的死亡率方面是独特的。Nm绕过了天然免疫的主要机制，如补体系统和吞噬作用。中性粒细胞胞外陷阱（NETs）是在全身感染过程中由中性粒细胞形成的，并被认为含有入侵的微生物。在这里，我们研究了Nm与NET的相互作用。脑膜炎球菌和自发释放的外膜囊泡（SOMV）都是有效的NET诱导剂。NET不能杀死NET结合的脑膜炎球菌，但减缓了它们的增殖速度。使用Nm作为模式生物，我们确定了细菌如何逃避NET介导的杀伤的三种新机制：（i）用磷酸乙醇胺修饰脑膜炎球菌LPS的脂质A保护Nm免受NET结合的组织蛋白酶G的影响;（ii）高亲和力锌摄取受体ZnuD的表达允许Nm逃避NET介导的营养免疫;（iii）SOMV与NET的结合使Nm免于NET结合和随后的抑菌作用。逃避NET可能导致脑膜炎球菌病的最快速进展。Nm在体内诱导NET形成可能会加重血管内血栓形成，最终导致弥散性血管内凝血（DIC）。
Neisseria meningitidis (Nm) is a leading cause of septicemia in childhood. Nm septicemia is unique with respect to very quick disease progression, high in vivo bacterial replication rate and its considerable mortality. Nm circumvents major mechanisms of innate immunity such as complement system and phagocytosis. Neutrophil extracellular traps (NETs) are formed from neutrophils during systemic infection and are suggested to contain invading microorganisms. Here, we investigated the interaction of Nm with NETs. Both, meningococci and spontaneously released outer membrane vesicles (SOMVs) were potent NET inducers. NETs were unable to kill NET bound meningococci, but slowed down their proliferation rate. Using Nm as model organism we identified three novel mechanisms how bacteria can evade NET-mediated killing: (i) modification of lipid A of meningococcal LPS with phosphoethanolamine protected Nm from NET-bound cathepsin G; (ii) expression of the high-affinity zinc uptake receptor ZnuD allowed Nm to escape NET-mediated nutritional immunity; (iii) binding of SOMVs to NETs saved Nm from NET binding and the consequent bacteriostatic effect. Escape from NETs may contribute to the most rapid progression of meningococcal disease. The induction of NET formation by Nm in vivo might aggravate thrombosis in vessels ultimately directing to disseminated intravascular coagulation (DIC).