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.

中文翻译：

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中性粒细胞胞外陷阱驱动疟疾的炎症发病机制。

中性粒细胞是重要的先天免疫细胞，在死亡时会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。我们证明血红素诱导的 NETs 对于疟疾发病机制至关重要。使用患者样本和小鼠模型，我们定义了 NET 介导的脉管系统炎症的两种机制：通过粒细胞集落刺激因子的产生激活紧急粒细胞生成，以及诱导内皮细胞粘附受体细胞间粘附分子-1。可溶性 NET 成分有助于隔离寄生虫并介导组织破坏。我们证明中性粒细胞在疟疾免疫病理学中发挥着关键作用，并提出抑制 NET 作为血管感染的治疗策略。