In neurological diseases, the actions of microglia, the resident myeloid cells of the CNS parenchyma, may diverge from, or intersect with, those of recruited monocytes to drive immune-mediated pathology. However, defining the precise roles of each cell type has historically been impeded by the lack of discriminating markers and experimental systems capable of accurately identifying them. Our ability to distinguish microglia from monocytes in neuroinflammation has advanced with single-cell technologies, new markers and drugs that identify and deplete them, respectively. Nevertheless, the focus of individual studies on particular cell types, diseases or experimental approaches has limited our ability to connect phenotype and function more widely and across diverse CNS pathologies. Here, we critically review, tabulate and integrate the disease-specific functions and immune profiles of microglia and monocytes to provide a comprehensive atlas of myeloid responses in viral encephalitis, demyelination, neurodegeneration and ischemic injury. In emphasizing the differential roles of microglia and monocytes in the severe neuroinflammatory disease of viral encephalitis, we connect inflammatory pathways common to equally incapacitating diseases with less severe inflammation. We examine these findings in the context of human studies and highlight the benefits and inherent limitations of animal models that may impede or facilitate clinical translation. This enables us to highlight common and contrasting, non-redundant and often opposing roles of microglia and monocytes in disease that could be targeted therapeutically.

在神经系统疾病中，小胶质细胞（中枢神经系统实质的常驻髓细胞）的作用可能与募集的单核细胞的作用不同或相交，以驱动免疫介导的病理学。然而，在历史上，由于缺乏能够准确识别它们的区分标记和实验系统，定义每种细胞类型的精确作用一直受到阻碍。我们在神经炎症中区分小胶质细胞和单核细胞的能力随着单细胞技术、新的标记物和分别识别和消除它们的药物的发展而进步。然而，对特定细胞类型、疾病或实验方法的个别研究的重点限制了我们更广泛地连接表型和功能并跨越多种 CNS 病理的能力。在这里，我们批判性地回顾，汇总并整合小胶质细胞和单核细胞的疾病特异性功能和免疫特征，以提供病毒性脑炎、脱髓鞘、神经变性和缺血性损伤中髓样反应的综合图谱。在强调小胶质细胞和单核细胞在病毒性脑炎的严重神经炎症性疾病中的不同作用时，我们将同样致残的疾病常见的炎症通路与不太严重的炎症联系起来。我们在人类研究的背景下检查这些发现，并强调可能阻碍或促进临床转化的动物模型的好处和固有局限性。这使我们能够突出小胶质细胞和单核细胞在疾病中的共同和对比、非冗余和经常相反的作用，这些作用可以作为治疗的靶点。