The liver connects the intestinal portal vasculature with the general circulation, using a diverse array of immune cells to protect from pathogens that translocate from the gut 1 . In liver lobules, blood flows from portal triads that are situated in periportal lobular regions to the central vein via a polarized sinusoidal network. Despite this asymmetry, resident immune cells in the liver are considered to be broadly dispersed across the lobule. This differs from lymphoid organs, in which immune cells adopt spatially biased positions to promote effective host defence 2 , 3 . Here we used quantitative multiplex imaging, genetic perturbations, transcriptomics, infection-based assays and mathematical modelling to reassess the relationship between the localization of immune cells in the liver and host protection. We found that myeloid and lymphoid resident immune cells concentrate around periportal regions. This asymmetric localization was not developmentally controlled, but resulted from sustained MYD88-dependent signalling induced by commensal bacteria in liver sinusoidal endothelial cells, which in turn regulated the composition of the pericellular matrix involved in the formation of chemokine gradients. In vivo experiments and modelling showed that this immune spatial polarization was more efficient than a uniform distribution in protecting against systemic bacterial dissemination. Together, these data reveal that liver sinusoidal endothelial cells sense the microbiome, actively orchestrating the localization of immune cells, to optimize host defence. The authors show that zonation extends to hepatic immune cells and that this spatial patterning is mediated by microbiome sensing by liver sinusoidal endothelial cells, and provide evidence that immune zonation is required to protect the host from the dissemination of blood-borne pathogens.

中文翻译：

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肝脏共生驱动的免疫分区促进宿主防御

肝脏将肠门脉管系统与全身循环连接起来，使用多种免疫细胞来保护免受从肠道 1 易位的病原体的侵害。在肝小叶中，血液从位于门静脉周围小叶区域的门静脉三联体通过极化的正弦网络流向中央静脉。尽管存在这种不对称性，但肝脏中的常驻免疫细胞被认为广泛分散在小叶中。这与淋巴器官不同，其中免疫细胞采用空间偏向位置来促进有效的宿主防御 2、3。在这里，我们使用定量多重成像、遗传扰动、转录组学、基于感染的分析和数学模型来重新评估免疫细胞在肝脏中的定位与宿主保护之间的关系。我们发现骨髓和淋巴常驻免疫细胞集中在门静脉周围区域。这种不对称定位不受发育控制，而是由肝窦内皮细胞中的共生细菌诱导的持续的 MYD88 依赖性信号传导引起的，这反过来又调节了参与趋化因子梯度形成的细胞周围基质的组成。体内实验和建模表明，这种免疫空间极化在防止全身细菌传播方面比均匀分布更有效。总之，这些数据表明肝窦内皮细胞感知微生物组，主动协调免疫细胞的定位，以优化宿主防御。