The immune cells of the central nervous system (CNS) comprise parenchymal microglia and at the CNS border regions meningeal, perivascular, and choroid plexus macrophages (collectively called CNS-associated macrophages, CAMs). While previous work has shown that microglial properties depend on environmental signals from the commensal microbiota, the effects of microbiota on CAMs are unknown. By combining several microbiota manipulation approaches, genetic mouse models, and single-cell RNA-sequencing, we have characterized CNS myeloid cell composition and function. Under steady-state conditions, the transcriptional profiles and numbers of choroid plexus macrophages were found to be tightly regulated by complex microbiota. In contrast, perivascular and meningeal macrophages were affected to a lesser extent. An acute perturbation through viral infection evoked an attenuated immune response of all CAMs in germ-free mice. We further assessed CAMs in a more chronic pathological state in 5xFAD mice, a model for Alzheimer’s disease, and found enhanced amyloid beta uptake exclusively by perivascular macrophages in germ-free 5xFAD mice. Our results aid the understanding of distinct microbiota–CNS macrophage interactions during homeostasis and disease, which could potentially be targeted therapeutically.

中文翻译：

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共生微生物群在稳态和疾病期间对哺乳动物中枢神经系统中的髓样亚群产生不同的影响

中枢神经系统 (CNS) 的免疫细胞包括实质小胶质细胞和在 CNS 边界区域的脑膜、血管周围和脉络丛巨噬细胞（统称为 CNS 相关巨噬细胞，CAM）。虽然之前的工作表明小胶质细胞的特性取决于来自共生微生物群的环境信号，但微生物群对 CAM 的影响尚不清楚。通过结合几种微生物群操作方法、遗传小鼠模型和单细胞 RNA 测序，我们表征了 CNS 髓样细胞的组成和功能。在稳态条件下，发现脉络丛巨噬细胞的转录谱和数量受到复杂微生物群的严格调控。相比之下，血管周围和脑膜巨噬细胞受到的影响较小。病毒感染引起的急性扰动引起了无菌小鼠中所有 CAM 的减弱的免疫反应。我们进一步评估了 5xFAD 小鼠（一种阿尔茨海默病模型）中处于更慢性病理状态的 CAM，并发现无菌 5xFAD 小鼠的血管周围巨噬细胞仅增强了淀粉样蛋白 β 的摄取。我们的结果有助于了解稳态和疾病期间不同的微生物群-中枢神经系统巨噬细胞相互作用，这可能成为治疗目标。