Neuroinvasion by simian immunodeficiency virus coincides with increased numbers of perivascular macrophages/microglia and intrathecal immune activation
Neuroinvasion by simian immunodeficiency virus coincides with increased numbers of perivascular macrophages/microglia and intrathecal immune activation
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DOI：
10.3109/13550289609146909
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发表时间：
1996-12-01
影响因子：
3.2
通讯作者：
Lackner, AA
中科院分区：
文献类型：
--
作者：
Lane, JH;Sasseville, VG;Lackner, AA
在高峰病毒血症和初始抗体应答期间，感染SIV致病性和非致病性分离株的恒河猴在病毒载量和组织分布方面表现出明显的差异。感染SIV致病性分离株的动物在接种后两周内脑脊液和脑实质中总是有病毒，而感染非致病性分离株的动物则没有。SIV和HIV神经侵袭的潜在机制尚不清楚，但经常提出从外周循环中招募潜伏感染的单核细胞（特洛伊木马理论）。循环单核细胞（血管周围巨噬细胞/小胶质细胞来源于此）可能是病毒穿过血脑屏障的细胞相关运输工具。这种运输和CNS中血管周围巨噬细胞/小胶质细胞周转的动力学可能依赖于内皮和白细胞粘附分子，如血管细胞粘附分子-1（VCAM-1），先前已显示其在SIV脑炎中在脑血管内皮上上调。为了研究外周血单核细胞募集到血管周围巨噬细胞/小胶质细胞池的作用，在最初的病毒神经侵袭的时候，我们研究了血管周围巨噬细胞/小胶质细胞密度，内皮细胞VCAM-1的表达和本地化的病毒核酸急性感染的猕猴的中枢神经系统的致病性和非致病性的SIV分子克隆之间的时间关系。同时检查CSF喹啉酸的浓度，这是鞘内免疫和巨噬细胞活化的标志物。我们发现，血管周围巨噬细胞/小胶质细胞密度的显着增加与病毒的神经侵袭和CSF喹啉酸的显着升高相一致。原位杂交和免疫组化结果显示，感染的血管周围细胞为巨噬细胞/小胶质细胞。这些发现提供的证据表明，神经侵袭是通过感染的单核细胞的流入发生的，这些单核细胞作为血管周围巨噬细胞/小胶质细胞驻留在CNS中。然而，VCAM-1表达与这些事件没有明确的相关性，因此其对初始病毒神经侵袭的贡献尚不清楚。
During peak viremia and initial antibody response, rhesus macaques infected with pathogenic and nonpathogenic isolates of SIV show distinct differences in viral load and tissue distribution. Animals infected with pathogenic isolates of SIV invariably have virus in the CSF and brain parenchyma by two weeks postinoculation, whereas animals infected with nonpathogenic isolates do not. Mechanisms underlying neuroinvasion by SIV and HIV are unknown, but recruitment of latently infected mononuclear cells from the peripheral circulation (Trojan horse theory) is frequently proposed, Circulating monocytes, from which perivascular macrophage/microglia are derived, are a likely vehicle for cell-associated transport of virus across the blood-brain barrier. This transport and the kinetics of perivascular macrophage/microglial turnover in the CNS likely depend on endothelial and leukocyte adhesion molecules such as vascular cell adhesion molecule-1 (VCAM-1), which has previously been shown to be upregulated on cerebrovascular endothelium in SIV encephalitis. To investigate the role of peripheral monocyte recruitment into the perivascular macrophage/microglial cell pool at the time of initial viral neuroinvasion, we examined the temporal relationships among perivascular macrophage/microglia density, endothelial VCAM-1 expression and localization of viral nucleic acid in the CNS of macaques acutely infected with pathogenic and nonpathogenic molecular clones of SIV. The concentration of CSF quinolinic acid, a marker of intrathecal immune and macrophage activation, was examined concurrently. We found that significant increases in the density of perivascular macrophages/microglia coincided with viral neuroinvasion and marked elevations in CSF quinolinic acid. Furthermore, combined in situ hybridization and immunohistochemistry demonstrated that infected perivascular cells were macrophages/microglia. These findings provide evidence suggesting that neuroinvasion occurs through an influx of infected monocytes which take up residence in the CNS as perivascular macrophages/microglia. VCAM-1 expression, however, was not clearly correlated with these events, thus its contribution to initial viral neuroinvasion is unclear.