Neutrophil extracellular traps drive inflammatory pathogenesis in malaria
Neutrophil extracellular traps drive inflammatory pathogenesis in malaria
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神经细胞外陷阱驱动疟疾的炎症发病机制
DOI：
10.1126/sciimmunol.aaw0336
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发表时间：
2019-10-01
影响因子：
24.8
通讯作者：
Amulic, Borko
中科院分区：
文献类型：
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作者：
Knackstedt, Sebastian Lorenz;Georgiadou, Athina;Amulic, Borko
中性粒细胞是一种重要的先天性免疫细胞，当它们死亡时，它们以中性粒细胞胞外陷阱（NET）的形式挤出染色质。这种形式的细胞死亡具有有效的免疫刺激活性。我们发现血红素诱导的NET是疟疾发病机制所必需的。使用患者样本和小鼠模型，我们定义了两种机制NET介导的炎症的血管系统：激活紧急粒细胞生成通过粒细胞集落刺激因子的生产和诱导内皮细胞粘附受体细胞间粘附分子-1。可溶性NET组分促进寄生虫隔离并介导组织破坏。我们证明了中性粒细胞在疟疾免疫病理学中起着关键作用，并提出了抑制NET作为血管感染的治疗策略。
Neutrophils are essential innate immune cells that extrude chromatin in the form of neutrophil extracellular traps (NETs) when they die. This form of cell death has potent immunostimulatory activity. We show that heme-induced NETs are essential for malaria pathogenesis. Using patient samples and a mouse model, we define two mechanisms of NET-mediated inflammation of the vasculature: activation of emergency granulopoiesis via granulocyte colony-stimulating factor production and induction of the endothelial cytoadhesion receptor intercellular adhesion molecule-1. Soluble NET components facilitate parasite sequestration and mediate tissue destruction. We demonstrate that neutrophils have a key role in malaria immunopathology and propose inhibition of NETs as a treatment strategy in vascular infections.