Department of Neurology and Curriculum in Neurobiology, University of North Carolina, CB #7025, 6109F Neuroscience Research Building 103 Mason Farm Road, Chapel Hill, NC 27599, USA.
Cell Tissue Res. 2012 Feb;347(2):443-55. doi: 10.1007/s00441-011-1301-8. Epub 2012 Jan 27.
Although lentiviruses such as human, feline and simian immunodeficiency viruses (HIV, FIV, SIV) rapidly gain access to cerebrospinal fluid (CSF), the mechanisms that control this entry are not well understood. One possibility is that the virus may be carried into the brain by immune cells that traffic across the blood-CSF barrier in the choroid plexus. Since few studies have directly examined macrophage trafficking across the blood-CSF barrier, we established transwell and explant cultures of feline choroid plexus epithelium and measured trafficking in the presence or absence of FIV. Macrophages in co-culture with the epithelium showed significant proliferation and robust trafficking that was dependent on the presence of epithelium. Macrophage migration to the apical surface of the epithelium was particularly robust in the choroid plexus explants where 3-fold increases were seen over the first 24 h. Addition of FIV to the cultures greatly increased the number of surface macrophages without influencing replication. The epithelium in the transwell cultures was also permissive to PBMC trafficking, which increased from 17 to 26% of total cells after exposure to FIV. Thus, the choroid plexus epithelium supports trafficking of both macrophages and PBMCs. FIV significantly enhanced translocation of macrophages and T cells indicating that the choroid plexus epithelium is likely to be an active site of immune cell trafficking in response to infection.
虽然慢病毒，如人类免疫缺陷病毒（HIV）、猫免疫缺陷病毒（FIV）和猴免疫缺陷病毒（SIV）能够迅速进入脑脊液（CSF），但其进入的机制尚不清楚。一种可能性是，病毒可能通过在脉络丛中穿过血脑屏障的免疫细胞进入大脑。由于很少有研究直接检测巨噬细胞在血脑屏障中的迁移，我们建立了猫脉络丛上皮细胞的 Transwell 和器官培养物，并在存在或不存在 FIV 的情况下测量了迁移。与上皮细胞共培养的巨噬细胞表现出明显的增殖和强大的迁移，这依赖于上皮细胞的存在。在脉络丛器官培养物中，巨噬细胞迁移到上皮细胞的顶端表面特别强烈，在前 24 小时内增加了 3 倍。将 FIV 添加到培养物中大大增加了表面巨噬细胞的数量，而不影响复制。Transwell 培养物中的上皮细胞也允许 PBMC 迁移，在暴露于 FIV 后，从总细胞的 17%增加到 26%。因此，脉络丛上皮细胞支持巨噬细胞和 PBMC 的迁移。FIV 显著增强了巨噬细胞和 T 细胞的易位，表明脉络丛上皮细胞可能是感染时免疫细胞迁移的活跃部位。
