Brown Amanda
Johns Hopkins University School of Medicine, 600 North Wolfe Street/Meyer 6-181, Baltimore, MD 21287 USA.
Clin Transl Med. 2015 Feb 26;4:7. doi: 10.1186/s40169-015-0049-2. eCollection 2015.
Tissue macrophages play important roles in maintaining homeostasis in most organs of the body including the brain where microglia represent the resident phagocytic cells of this compartment. The possibility of one day harnessing macrophage plasticity to treat or ameliorate disorders including obesity, cancer, organ damage, intestinal disorders, neurodegeneration, and cardiovascular disease in which these cells play a role, is a very exciting prospect. Inflammatory signaling is required for regenerative repair, healing, and pathogen clearance functions. However, when the inflammatory response persists in a chronic fashion over an extended period of time, damage to neurons is followed by neuronal injury and dysfunction. Macrophages in the brain are heterogeneous arising from tissues during embryogenesis, and in the adult, from bone marrow derived monocytes that enter through the blood-brain-barrier. While much of our insight regarding macrophage functional subtypes has been garnered through elegant studies in mice, which are amenable to genetic manipulation, far less is known about such cells in human tissues, and particularly in the brain under normal, disease, or injurious conditions. In this regard, non-human primate models for human immunodeficiency virus have been extremely useful for understanding the contribution of bone marrow-derived monocytes in neurological disease and their interaction and impact on the activation state of resident microglia in the brain. This review will focus on what has been learned from the rhesus macaque models about the types of macrophages present in the brains of animals with encephalitis. In vitro studies, which have used human blood monocytes differentiated into macrophages to address the question of macrophage subsets in HIV infection will be highlighted. Recent insights on macrophage phenotype and persistent inflammation in the brain in HIV-associated neurocognitive disorder from immunohistochemical studies on human autopsy tissue will be examined.
组织巨噬细胞在维持身体大多数器官的内环境稳定中发挥着重要作用，包括大脑，其中小胶质细胞是该区域的常驻吞噬细胞。有朝一日利用巨噬细胞可塑性来治疗或改善包括肥胖、癌症、器官损伤、肠道疾病、神经退行性变和心血管疾病等这些细胞在其中起作用的疾病，是一个非常令人兴奋的前景。炎症信号对于再生修复、愈合和病原体清除功能是必需的。然而，当炎症反应在较长时间内以慢性方式持续存在时，神经元损伤之后会出现神经元功能障碍。大脑中的巨噬细胞具有异质性，在胚胎发育过程中起源于组织，在成体中则起源于通过血脑屏障进入的骨髓来源的单核细胞。虽然我们对巨噬细胞功能亚型的许多认识是通过对易于进行基因操作的小鼠的精细研究获得的，但对于人类组织中的此类细胞，尤其是在正常、疾病或损伤状态下的大脑中的细胞，我们了解得要少得多。在这方面，人类免疫缺陷病毒的非人灵长类动物模型对于理解骨髓来源的单核细胞在神经疾病中的作用以及它们与大脑中常驻小胶质细胞激活状态的相互作用和影响非常有用。本综述将重点关注从恒河猴模型中了解到的关于患有脑炎的动物大脑中存在的巨噬细胞类型的信息。将突出强调使用分化为巨噬细胞的人血单核细胞来解决HIV感染中巨噬细胞亚群问题的体外研究。还将研究从对人类尸检组织的免疫组织化学研究中获得的关于HIV相关神经认知障碍中巨噬细胞表型和大脑中持续炎症的最新见解。
Zotero 插件
