In adults, liver-resident macrophages, or Kupffer cells (KCs), reside in the sinusoids and sterilize circulating blood by capturing rapidly flowing microbes. We developed quantitative intravital imaging of 1-day-old mice combined with transcriptomics, genetic manipulation, and in vivo infection assays to interrogate increased susceptibility of newborns to bloodstream infections. Whereas 1-day-old KCs were better at catching Escherichia coli in vitro, we uncovered a critical 1-week window postpartum when KCs have limited access to blood and must translocate from liver parenchyma into the sinusoids. KC migration was independent of the microbiome but depended on macrophage migration inhibitory factor, its receptor CD74, and the adhesion molecule CD44. On the basis of our findings, we propose a model of progenitor macrophage seeding of the liver sinusoids via a reverse transmigration process from liver parenchyma. These results also illustrate the importance of developing newborn mouse models to understand newborn immunity and disease.

中文翻译：

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Kupffer 细胞反向迁移到肝窦可减轻新生儿败血症和脑膜炎


在成人中，肝脏驻留的巨噬细胞或库普弗细胞 （KC） 驻留在鼻窦中，并通过捕获快速流动的微生物对循环血液进行消毒。我们开发了 1 日龄小鼠的定量活体成像，结合转录组学、基因操作和体内感染测定，以询问新生儿对血流感染的易感性增加。虽然 1 日龄的 KC 在体外捕获大肠杆菌方面效果更好，但我们发现了一个关键的产后 1 周窗口，此时 KC 获得血液的机会有限，必须从肝实质转移到鼻窦中。KC 迁移独立于微生物组，但取决于巨噬细胞迁移抑制因子、其受体 CD74 和粘附分子 CD44。根据我们的研究结果，我们提出了一种通过肝实质的反向轮回过程将肝窦的祖细胞巨噬细胞接种的模型。这些结果还说明了开发新生小鼠模型以了解新生免疫和疾病的重要性。