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Organism-Level Analysis of Vaccination Reveals Networks of Protection across Tissues.
Cell ( IF 45.5 ) Pub Date : 2017-Oct-05 , DOI: 10.1016/j.cell.2017.08.024
Motohiko Kadoki 1 , Ashwini Patil 2 , Cornelius C Thaiss 1 , Donald J Brooks 1 , Surya Pandey 1 , Deeksha Deep 1 , David Alvarez 3 , Ulrich H von Andrian 3 , Amy J Wagers 4 , Kenta Nakai 2 , Tarjei S Mikkelsen 4 , Magali Soumillon 4 , Nicolas Chevrier 1
Affiliation  

A fundamental challenge in immunology is to decipher the principles governing immune responses at the whole-organism scale. Here, using a comparative infection model, we observe immune signal propagation within and between organs to obtain a dynamic map of immune processes at the organism level. We uncover two inter-organ mechanisms of protective immunity mediated by soluble and cellular factors. First, analyzing ligand-receptor connectivity across tissues reveals that type I IFNs trigger a whole-body antiviral state, protecting the host within hours after skin vaccination. Second, combining parabiosis, single-cell analyses, and gene knockouts, we uncover a multi-organ web of tissue-resident memory T cells that functionally adapt to their environment to stop viral spread across the organism. These results have implications for manipulating tissue-resident memory T cells through vaccination and open up new lines of inquiry for the analysis of immune responses at the organism level.

中文翻译:

疫苗接种的有机体水平分析揭示了跨组织的保护网络。

免疫学的一个基本挑战是破译在整个有机体范围内控制免疫反应的原理。在这里,使用比较感染模型,我们观察器官内和器官之间的免疫信号传播,以获得生物体水平的免疫过程动态图。我们揭示了两种由可溶性和细胞因子介导的保护性免疫的器官间机制。首先,分析组织间的配体-受体连接表明 I 型 IFN 触发全身抗病毒状态,在皮肤疫苗接种后数小时内保护宿主。其次,结合联体共生、单细胞分析和基因敲除,我们发现了组织驻留记忆 T 细胞的多器官网络,这些细胞在功能上适应其环境以阻止病毒在生物体中传播。
更新日期:2017-09-21
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