In vivo imaging of inflammasome activation reveals a subcapsular macrophage burst response that mobilizes innate and adaptive immunity
In vivo imaging of inflammasome activation reveals a subcapsular macrophage burst response that mobilizes innate and adaptive immunity
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DOI：
10.1038/nm.4016
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发表时间：
2016-01-01
期刊：
影响因子：
82.9
通讯作者：
Bousso, Philippe
中科院分区：
文献类型：
--
作者：
Sagoo, Pervinder;Garcia, Zacarias;Bousso, Philippe
炎症小体在对多种病原体的反应中被激活，并在形成适应性免疫中发挥重要作用，但体内炎症小体激活的时空协调及其促进有效免疫反应的机制尚不完全清楚。利用体内报告器可视化炎症小体组装，我们建立了炎症小体对局部病毒感染反应的分布、动力学和传播。我们发现，修饰的安卡拉牛痘病毒诱导囊下窦（SCS）巨噬细胞的炎性小体活化，紧接着是细胞死亡和细胞外ASC斑点的释放。淋巴结中这种短暂的炎性小体信号产生了大量炎症细胞的涌入，并从循环中动员T细胞来增加T细胞反应的强度。我们提出，在感染后，SCS巨噬细胞传递炎症小体活性和细胞死亡的爆发反应，转化为T细胞反应的扩大，确定炎症小体驱动的疫苗接种策略的一个重要方面。
The inflammasome is activated in response to a variety of pathogens and has an important role in shaping adaptive immunity, yet the spatiotemporal orchestration of inflammasome activation in vivo and the mechanisms by which it promotes an effective immune response are not fully understood. Using an in vivo reporter to visualize inflammasome assembly, we establish the distribution, kinetics and propagation of the inflammasome response to a local viral infection. We show that modified vaccinia Ankara virus induces inflammasome activation in subcapsular sinus (SCS) macrophages, which is immediately followed by cell death and release of extracellular ASC specks. This transient inflammasome signaling in the lymph node generates a robust influx of inflammatory cells and mobilizes T cells from the circulation to increase the magnitude of T cell responses. We propose that after infection, SCS macrophages deliver a burst response of inflammasome activity and cell death that translates into the broadening of T cell responses, identifying an important aspect of inflammasome-driven vaccination strategies.