Williams Kenneth C, Hickey William F
Department of Medicine, Harvard Medical School Division of Viral Pathogenesis Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
Annu Rev Neurosci. 2002;25:537-62. doi: 10.1146/annurev.neuro.25.112701.142822. Epub 2002 Mar 27.
This review focuses on the role of the extended macrophage/monocyte family in the central nervous system during HIV or SIV infection. The accumulated data, buttressed by recent experimental results, suggest that these cells play a central, pathogenic role in retroviral-associated CNS disease. While the immune system is able to combat the underlying retroviral infection, the accumulation and widespread activation of macrophages, microglia, and perivascular cells in the CNS are held in check. However, with the collapse of the immune system and the disappearance of the CD4(+) T cell population, productive infection reemerges, especially in CNS macrophages. These cells, as well as noninfected macrophages, are stimulated to high levels of activation. When members of this cell group become highly activated, they elaborate a wide spectrum of deleterious substances into the neural parenchyma. In the final phases of HIV or SIV infection, this chronic, widespread, and dramatic level of macrophage/monocyte/microglial activation constitutes a self-sustaining state of macrophage dysregulation, which results in pathological alterations and the emergence of various neurological problems.
本综述聚焦于HIV或SIV感染期间,巨噬细胞/单核细胞扩展家族在中枢神经系统中的作用。近期实验结果所支持的累积数据表明,这些细胞在逆转录病毒相关的中枢神经系统疾病中发挥着核心致病作用。虽然免疫系统能够对抗潜在的逆转录病毒感染,但中枢神经系统中巨噬细胞、小胶质细胞和血管周围细胞的积累及广泛激活受到抑制。然而,随着免疫系统的崩溃和CD4(+) T细胞群体的消失,尤其是在中枢神经系统巨噬细胞中,病毒复制性感染再次出现。这些细胞以及未感染的巨噬细胞被刺激到高水平的激活状态。当该细胞群体的成员被高度激活时,它们会向神经实质中释放多种有害物质。在HIV或SIV感染的最后阶段,这种慢性、广泛且显著的巨噬细胞/单核细胞/小胶质细胞激活状态构成了一种自我维持的巨噬细胞失调状态,导致病理改变和各种神经问题的出现。