Neutrophil Extracellular Traps in Periodontitis: A Web of Intrigue
Neutrophil Extracellular Traps in Periodontitis: A Web of Intrigue
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DOI：
10.1177/0022034515609097
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发表时间：
2016-01-01
影响因子：
7.6
通讯作者：
Chapple, I. L. C.
中科院分区：
文献类型：
--
作者：
White, P. C.;Chicca, I. J.;Chapple, I. L. C.
神经细胞外陷阱（NET）代表了嗜中性粒细胞介导的免疫的新范式。NET被认为构成高度保守的抗微生物策略，其包含被挤出到细胞外空间中的解致密的核DNA和相关的组蛋白。与网状DNA链相关的是一系列抗菌肽（AMP），其有助于细胞外破坏被截留在NET内的微生物。NET可以由保持活力的细胞或在称为NETosis的独特形式的程序性细胞死亡后释放，其依赖于活性氧（ROS）的产生和肽基精氨酸脱亚胺酶-4催化的核DNA的解浓缩。NET是针对一系列病原体（包括细菌、病毒、真菌和原生动物）以及宿主来源的介体而产生的。然而，NET的释放并非没有代价，因为伴随的细胞毒性分子的释放也会导致宿主组织损伤。许多免疫介导的疾病证明了这一点，其中过量或功能失调的NET产生，细菌NET逃避和NET清除减少与疾病发病机制相关。牙周炎是人类最常见的感染性炎症性疾病，其特征在于龈下菌斑生物膜内对特定细菌物种的嗜酸性反应失调。中性粒细胞是参与牙周炎的主要炎性细胞，并且先前已经发现在慢性牙周炎患者中就ROS产生而言表现出过度活跃和高反应性。然而，ROS依赖性NET形成对牙周健康或疾病的贡献仍不清楚。在这篇重点综述中，我们讨论了NET生产的机制、刺激和要求; NET-DNA和NET相关AMP捕获和杀死病原体的能力;以及NET在疾病中的潜在免疫原性。我们还推测了NETs在牙周炎发病机制中的潜在作用。
Neutrophil extracellular traps (NETs) represent a novel paradigm in neutrophil-mediated immunity. NETs are believed to constitute a highly conserved antimicrobial strategy comprising decondensed nuclear DNA and associated histones that are extruded into the extracellular space. Associated with the web-like strands of DNA is an array of antimicrobial peptides (AMPs), which facilitate the extracellular destruction of microorganisms that become entrapped within the NETs. NETs can be released by cells that remain viable or following a unique form of programmed cell death known as NETosis, which is dependent on the production of reactive oxygen species (ROS) and the decondensing of the nuclear DNA catalyzed by peptidyl arginine deiminase-4. NETs are produced in response to a range of pathogens, including bacteria, viruses, fungi, and protozoa, as well as host-derived mediators. NET release is, however, not without cost, as the concomitant release of cytotoxic molecules can also cause host tissue damage. This is evidenced by a number of immune-mediated diseases, in which excess or dysfunctional NET production, bacterial NET evasion, and decreased NET removal are associated with disease pathogenesis. Periodontitis is the most prevalent infectious-inflammatory disease of humans, characterized by a dysregulated neutrophilic response to specific bacterial species within the subgingival plaque biofilm. Neutrophils are the predominant inflammatory cell involved in periodontitis and have previously been found to exhibit hyperactivity and hyperreactivity in terms of ROS production in chronic periodontitis patients. However, the contribution of ROS-dependent NET formation to periodontal health or disease remains unclear. In this focused review, we discuss the mechanisms, stimuli, and requirements for NET production; the ability of NET-DNA and NET-associated AMPs to entrap and kill pathogens; and the potential immunogenicity of NETs in disease. We also speculate on the potential role of NETs in the pathogenesis of periodontitis.