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Microglia response following acute demyelination is heterogeneous and limits infiltrating macrophage dispersion.
Science Advances ( IF 13.6 ) Pub Date : 2020-01-15 , DOI: 10.1126/sciadv.aay6324 Jason R Plemel 1, 2, 3 , Jo Anne Stratton 1 , Nathan J Michaels 1 , Khalil S Rawji 1 , Eric Zhang 1 , Sarthak Sinha 4 , Charbel S Baaklini 2, 3 , Yifei Dong 1 , Madelene Ho 2 , Kevin Thorburn 5 , Timothy N Friedman 2 , Sana Jawad 1 , Claudia Silva 1 , Andrew V Caprariello 1 , Vahid Hoghooghi 1 , Julie Yue 2 , Arzina Jaffer 4 , Kelly Lee 2 , Bradley J Kerr 2, 6 , Raj Midha 1 , Peter K Stys 1 , Jeff Biernaskie 1, 4 , V Wee Yong 1
Science Advances ( IF 13.6 ) Pub Date : 2020-01-15 , DOI: 10.1126/sciadv.aay6324 Jason R Plemel 1, 2, 3 , Jo Anne Stratton 1 , Nathan J Michaels 1 , Khalil S Rawji 1 , Eric Zhang 1 , Sarthak Sinha 4 , Charbel S Baaklini 2, 3 , Yifei Dong 1 , Madelene Ho 2 , Kevin Thorburn 5 , Timothy N Friedman 2 , Sana Jawad 1 , Claudia Silva 1 , Andrew V Caprariello 1 , Vahid Hoghooghi 1 , Julie Yue 2 , Arzina Jaffer 4 , Kelly Lee 2 , Bradley J Kerr 2, 6 , Raj Midha 1 , Peter K Stys 1 , Jeff Biernaskie 1, 4 , V Wee Yong 1
Affiliation
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.
中文翻译:
急性脱髓鞘后的小胶质细胞反应是异质的,并限制了浸润性巨噬细胞的分散。
小胶质细胞和浸润性巨噬细胞被认为可以协调中枢神经系统对损伤的反应。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。我们对小胶质细胞和中枢神经系统相关的巨噬细胞进行了基因标记,以区别于浸润性巨噬细胞。使用单细胞RNA测序,我们描述了多个小胶质细胞激活状态,其中之一被丰富了干扰素相关的信号。尽管血液来源的巨噬细胞会急性浸润脱髓鞘病变,但小胶质细胞会逐渐垄断病变环境,使其包围浸润的巨噬细胞。在没有小胶质细胞的坐骨神经中,浸润性巨噬细胞反应得以持续。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占主导地位。小胶质细胞消融逆转了脱髓鞘脊髓对巨噬细胞的空间限制,突显了未实现的巨噬细胞与小胶质细胞的相互作用。小胶质细胞对周围炎症的限制可能是CNS维持其“免疫特权”状态的先前未知的机制。
更新日期:2020-01-16
中文翻译:
急性脱髓鞘后的小胶质细胞反应是异质的,并限制了浸润性巨噬细胞的分散。
小胶质细胞和浸润性巨噬细胞被认为可以协调中枢神经系统对损伤的反应。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。我们对小胶质细胞和中枢神经系统相关的巨噬细胞进行了基因标记,以区别于浸润性巨噬细胞。使用单细胞RNA测序,我们描述了多个小胶质细胞激活状态,其中之一被丰富了干扰素相关的信号。尽管血液来源的巨噬细胞会急性浸润脱髓鞘病变,但小胶质细胞会逐渐垄断病变环境,使其包围浸润的巨噬细胞。在没有小胶质细胞的坐骨神经中,浸润性巨噬细胞反应得以持续。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占主导地位。小胶质细胞消融逆转了脱髓鞘脊髓对巨噬细胞的空间限制,突显了未实现的巨噬细胞与小胶质细胞的相互作用。小胶质细胞对周围炎症的限制可能是CNS维持其“免疫特权”状态的先前未知的机制。