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| Advances of immunological pathogenesis research in HIV related neurocognitive disorder |
| JI Yongjia1, LU Hongzhou1,2 |
1. Department of Infectious Diseases, Shanghai Public Health Clinical Center, Shanghai 201508, China;
2. Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, China |
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Abstract With extended life of HIV-infected patients due to highly active anti-retroviral therapy (HAART), the rate of HIV associated neurocognitive disorder (HAND) remains high and attracts much attention. The evidence is clear that cytokines are elevated in the blood of patients with HIV infection, which contribute to elevating the permeability of blood-brain barrier. Benefiting from that, cells in the brain are infected with HIV that has accelerated through the blood-brain barrier both as cell-free virus and infected immune cells including monocytes and T cells. Upon migration into the central nervous system, HIV-infected monocytes and T cells not only infect brain resident cells but also produce proinflammatory cytokines such as TNF and IL-1ß, which further activate microglia and astrocytes. These activated brain glial cells and perivascular macrophages, which release inflammatory mediators, are the main contributors to neuroinflammation resulting in neuronal dysfunction. The pathogenesis of HAND is multifaceted, however, mounting evidence indicates that HIV related neuroinflammation plays a major role, which should be the focus of therapeutic research for HAND in future.
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Received: 11 January 2016
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人类免疫缺陷病毒感染相关神经认知功能障碍的免疫学发病机制研究进展
随着HIV感染者接受高效抗逆转录病毒治疗后生存时间延长，HIV感染相关神经认知功能障碍（HAND）引起广泛关注。研究证据表明，HIV感染过程中各种细胞因子上调，导致血脑屏障通透性上升。受益于此，外周游离HIV病毒以及被HIV感染的免疫细胞（单核/巨噬细胞、T淋巴细胞）可加速穿越血脑屏障进入中枢神经系统，并导致中枢神经细胞感染HIV。此外，HIV感染的单核/巨噬细胞或T淋巴细胞进入中枢系统后还分泌多种促炎性细胞因子如TNF、IL-1ß等激活小胶质细胞以及星形胶质细胞。脑胶质细胞被激活后与血管周围外来巨噬细胞等免疫细胞共同作用分泌炎症介质，导致HIV感染相关中枢神经系统炎症以及神经功能损伤。HAND发病尽管受多种因素影响，但越来越多证据表明，HIV相关神经炎症反应是导致HIV感染者出现神经认知功能以及行为异常最重要的原因，未来应当围绕于此进行HAND相关治疗研究。本文就近年来HAND免疫发病机制相关研究进展做一综述。
关键词：
HIV感染/并发症,
认知障碍/病因学,
认知障碍/病理生理学,
神经系统/病理生理学,
免疫,
综述
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