Hotchkiss Brain Institute and Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
Neuroscience and Mental Health Institute, University of Alberta, Edmonton, Alberta, Canada.
Sci Adv. 2020 Jan 15;6(3):eaay6324. doi: 10.1126/sciadv.aay6324. eCollection 2020 Jan.
Microglia and infiltrating macrophages are thought to orchestrate the central nervous system (CNS) response to injury; however, the similarities between these cells make it challenging to distinguish their relative contributions. We genetically labeled microglia and CNS-associated macrophages to distinguish them from infiltrating macrophages. Using single-cell RNA sequencing, we describe multiple microglia activation states, one of which was enriched for interferon associated signaling. Although blood-derived macrophages acutely infiltrated the demyelinated lesion, microglia progressively monopolized the lesion environment where they surrounded infiltrating macrophages. In the microglia-devoid sciatic nerve, the infiltrating macrophage response was sustained. In the CNS, the preferential proliferation of microglia and sparse microglia death contributed to microglia dominating the lesion. Microglia ablation reversed the spatial restriction of macrophages with the demyelinated spinal cord, highlighting an unrealized macrophages-microglia interaction. The restriction of peripheral inflammation by microglia may be a previously unidentified mechanism by which the CNS maintains its "immune privileged" status.
小胶质细胞和浸润巨噬细胞被认为是中枢神经系统（CNS）损伤反应的协调者；然而，这些细胞之间的相似性使得区分它们的相对贡献具有挑战性。我们通过基因标记小胶质细胞和与 CNS 相关的巨噬细胞来将它们与浸润巨噬细胞区分开来。通过单细胞 RNA 测序，我们描述了多个小胶质细胞激活状态，其中一种状态富集了与干扰素相关的信号。尽管血液衍生的巨噬细胞急性浸润脱髓鞘病变，但小胶质细胞逐渐垄断了病变环境，包围了浸润的巨噬细胞。在小胶质细胞缺失的坐骨神经中，浸润的巨噬细胞反应持续存在。在 CNS 中，小胶质细胞的优先增殖和稀疏的小胶质细胞死亡导致小胶质细胞主导病变。小胶质细胞消融逆转了脱髓鞘脊髓中巨噬细胞的空间限制，突出了一种未被认识的巨噬细胞-小胶质细胞相互作用。小胶质细胞对周围炎症的限制可能是 CNS 维持其“免疫特权”状态的一种以前未被识别的机制。
