Dickson D W, Lee S C, Mattiace L A, Yen S H, Brosnan C
Department of Pathology (Neuropathology), Albert Einstein College of Medicine, Bronx, New York 10461.
Glia. 1993 Jan;7(1):75-83. doi: 10.1002/glia.440070113.
Microglia are associated with central nervous system (CNS) pathology of both Alzheimer's disease (AD) and the acquired immunodeficiency syndrome (AIDS). In AD, microglia, especially those associated with amyloid deposits, have a phenotype that is consistent with a state of activation, including immunoreactivity with antibodies to class II major histocompatibility antigens and to inflammatory cytokines (interleukin-1-beta and tumor necrosis factor-alpha). Evidence from other studies in rodents indicate that microglia can be activated by neuronal degeneration. These results suggest that microglial activation in AD may be secondary to neurodegeneration and that, once activated, microglia may participate in a local inflammatory cascade that promotes tissue damage and contributes to amyloid formation. In AIDS, microglia are the primary target of retroviral infection. Both ramified and ameboid microglia, in addition to multinucleated giant cells, are infected by the human immunodeficiency virus (HIV-1). The mechanism of microglial infection is not known since microglia lack CD4, the HIV-1 receptor. Microglia display high affinity receptors for immunoglobulins, which makes antibody-mediated viral uptake a possible mechanism of infection. In AIDS, the extent of active viral infection and cytokine production may be critically dependent upon other factors, such as the presence of coinfecting agents. In the latter circumstance, very severe CNS pathology may emerge, including necrotizing lesions. In other circumstances, HIV infection of microglia probably leads to CNS pathology by indirect mechanisms, including release of viral proteins (gp120) and toxic cytokines. Such a mechanism is the best hypothesis for the pathogenesis of vacuolar myelopathy in adults and the diffuse gliosis that characterizes pediatric AIDS, in which very little viral antigen can be detected.
小胶质细胞与阿尔茨海默病（AD）和获得性免疫缺陷综合征（AIDS）的中枢神经系统（CNS）病理学有关。在AD中，小胶质细胞，尤其是那些与淀粉样蛋白沉积相关的小胶质细胞，具有与激活状态一致的表型，包括与II类主要组织相容性抗原抗体和炎性细胞因子（白细胞介素-1-β和肿瘤坏死因子-α）的免疫反应性。来自啮齿动物的其他研究证据表明，小胶质细胞可被神经元变性激活。这些结果表明，AD中的小胶质细胞激活可能继发于神经变性，并且一旦被激活，小胶质细胞可能参与局部炎症级联反应，促进组织损伤并有助于淀粉样蛋白形成。在AIDS中，小胶质细胞是逆转录病毒感染的主要靶标。除了多核巨细胞外，分枝状和阿米巴样小胶质细胞均被人类免疫缺陷病毒（HIV-1）感染。由于小胶质细胞缺乏HIV-1受体CD4，因此小胶质细胞感染的机制尚不清楚。小胶质细胞显示出对免疫球蛋白的高亲和力受体，这使得抗体介导的病毒摄取成为一种可能的感染机制。在AIDS中，活跃的病毒感染和细胞因子产生的程度可能严重依赖于其他因素，例如合并感染因子的存在。在后一种情况下，可能会出现非常严重的CNS病理学，包括坏死性病变。在其他情况下，小胶质细胞的HIV感染可能通过间接机制导致CNS病理学，包括病毒蛋白（gp120）和毒性细胞因子的释放。这种机制是成人空泡性脊髓病发病机制和小儿AIDS特征性弥漫性胶质增生的最佳假设，在小儿AIDS中几乎检测不到病毒抗原。
