Understanding the MIND phenotype: macrophage/microglia inflammation in neurocognitive disorders related to human immunodeficiency virus infection.
Understanding the MIND phenotype: macrophage/microglia inflammation in neurocognitive disorders related to human immunodeficiency virus infection.
复制标题
DOI：
10.1186/s40169-015-0049-2
复制
发表时间：
2015
影响因子：
10.6
通讯作者：
Brown A
中科院分区：
文献类型：
--
作者：
Brown A
组织巨噬细胞在维持身体大部分器官（包括脑）的体内平衡方面发挥重要作用，其中小胶质细胞代表该隔室的常驻吞噬细胞。有一天利用巨噬细胞的可塑性来治疗或改善包括肥胖、癌症、器官损伤、肠道疾病、神经变性和心血管疾病在内的疾病的可能性，这些细胞在其中发挥作用，是一个非常令人兴奋的前景。炎症信号传导是再生修复、愈合和病原体清除功能所必需的。然而，当炎症反应以慢性方式持续一段延长的时间时，神经元损伤之后是神经元损伤和功能障碍。脑中的巨噬细胞是异质性的，在胚胎发育期间由组织产生，并且在成人中由通过血脑屏障进入的骨髓来源的单核细胞产生。虽然我们对巨噬细胞功能亚型的许多见解都是通过对小鼠的优雅研究获得的，这些研究适合遗传操作，但对人体组织中的此类细胞知之甚少，特别是在正常，疾病或损伤条件下的大脑中。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系统疾病中的作用及其对大脑中常驻小胶质细胞活化状态的相互作用和影响非常有用。这篇综述将集中于从恒河猴模型中了解到的关于脑炎动物脑中存在的巨噬细胞类型的信息。在体外研究中，使用人血单核细胞分化成巨噬细胞，以解决艾滋病毒感染中的巨噬细胞亚群的问题将得到强调。最近的见解巨噬细胞表型和持续性炎症在大脑中的艾滋病毒相关的神经认知障碍，从人类尸检组织的免疫组织化学研究将进行检查。本文的在线版本（doi：10.1186/s40169-015-0049-2）包含补充材料，可供授权用户使用。
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. The online version of this article (doi:10.1186/s40169-015-0049-2) contains supplementary material, which is available to authorized users.