Discipline of Pathology, Faculty of Medicine and Health, School of Medical Sciences, The University of Sydney, Sydney, NSW, Australia.
Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia.
Front Immunol. 2020 Dec 8;11:600822. doi: 10.3389/fimmu.2020.600822. eCollection 2020.
Inflammation of the brain parenchyma is characteristic of neurodegenerative, autoimmune, and neuroinflammatory diseases. During this process, microglia, which populate the embryonic brain and become a permanent sentinel myeloid population, are inexorably joined by peripherally derived monocytes, recruited by the central nervous system. These cells can quickly adopt a morphology and immunophenotype similar to microglia. Both microglia and monocytes have been implicated in inducing, enhancing, and/or maintaining immune-mediated pathology and thus disease progression in a number of neuropathologies. For many years, experimental and analytical systems have failed to differentiate resident microglia from peripherally derived myeloid cells accurately. This has impeded our understanding of their precise functions in, and contributions to, these diseases, and hampered the development of novel treatments that could target specific cell subsets. Over the past decade, microglia have been investigated more intensively in the context of neuroimmunological research, fostering the development of more precise experimental systems. In light of our rapidly growing understanding of these cells, we discuss the differential origins of microglia and peripherally derived myeloid cells in the inflamed brain, with an analysis of the problems resolving these cell types phenotypically and morphologically, and highlight recent developments enabling more precise identification.
脑实质的炎症是神经退行性、自身免疫和神经炎症性疾病的特征。在这个过程中，胚胎大脑中存在的小胶质细胞成为永久性的髓系细胞哨兵，并不可避免地与外周衍生的单核细胞结合，这些单核细胞被中枢神经系统募集。这些细胞可以迅速采用类似于小胶质细胞的形态和免疫表型。小胶质细胞和单核细胞都被认为在多种神经病理学中诱导、增强和/或维持免疫介导的病理，从而促进疾病进展。多年来，实验和分析系统未能准确地区分驻留的小胶质细胞和外周衍生的髓系细胞。这阻碍了我们对它们在这些疾病中的精确功能和贡献的理解，并阻碍了开发可以针对特定细胞亚群的新治疗方法。在过去的十年中，小胶质细胞在神经免疫研究的背景下得到了更深入的研究，促进了更精确的实验系统的发展。鉴于我们对这些细胞的理解迅速增长，我们讨论了在炎症大脑中小胶质细胞和外周衍生的髓系细胞的不同起源，并分析了在表型和形态上区分这些细胞类型所存在的问题，并强调了最近的一些发展，这些发展使得更精确的鉴定成为可能。
