NK cells promote neutrophil recruitment in the brain during sepsis-induced neuroinflammation.
NK cells promote neutrophil recruitment in the brain during sepsis-induced neuroinflammation.
复制标题
在脓毒症引起的神经炎症期间，NK 细胞促进大脑中中性粒细胞的募集
DOI：
10.1038/srep27711
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发表时间：
2016-06-08
影响因子：
4.6
通讯作者：
Tang H
中科院分区：
文献类型：
--
作者：
He H;Geng T;Chen P;Wang M;Hu J;Kang L;Song W;Tang H
脓毒症可影响中枢神经系统，从而导致神经炎症，进而导致脑损伤或功能障碍。然而，脓毒症时神经炎性反应的发生机制尚不清楚。通过给小鼠注射脂多糖(LPS)模拟脓毒症，我们发现在血脑屏障开放后不久，常规的CD11b+CD27+NK亚群迁移到脑内，随后中性粒细胞浸润。有趣的是，在内毒素治疗之前，NK细胞的耗尽严重损害了炎症大脑中中性粒细胞的募集。在活体募集实验中，我们发现脑渗透的NK细胞对中性粒细胞具有趋化活性，这依赖于CXCL2等趋化因子的高表达。此外，小胶质细胞也负责中性粒细胞的募集，其趋化活性因NK细胞的消融而显著受损。此外，去除NK细胞可以显著改善内毒素处理的小鼠的抑郁样行为。这些数据表明，NK细胞调节的中性粒细胞在被指责的大脑中重新聚集，这也可以在另一种脓毒症模型上看到，盲肠结扎和穿孔。因此，我们的发现揭示了脓毒症诱导的神经炎症发生的一个重要场景。
Sepsis could affect the central nervous system and thus induces neuroinflammation, which subsequently leads to brain damage or dysfunction. However, the mechanisms of generation of neuroinflammation during sepsis remain poorly understood. By administration of lipopolysaccharides (LPS) in mice to mimic sepsis, we found that shortly after opening the blood–brain barrier, conventional CD11b+CD27+NK subset migrated into the brain followed by subsequent neutrophil infiltration. Interestingly, depletion of NK cells prior to LPS treatment severely impaired neutrophil recruitment in the inflamed brain. Byin vivorecruitment assay, we found that brain-infiltrated NK cells displayed chemotactic activity to neutrophils, which depended on the higher expression of chemokines such as CXCL2. Moreover, microglia were also responsible for neutrophil recruitment and their chemotactic activity was significantly impaired by ablation of NK cells. Furthermore, depletion of NK cells could significantly ameliorate depression-like behavior in LPS-treated mice. These data indicated a NK cell-regulated neutrophil recruitment in the blamed brain, which also could be seen on another sepsis model, cecal ligation and puncture. So, our findings revealed an important scenario in the generation of sepsis-induced neuroinflammation.