We previously showed that rhesus macaques neonatally infected with simian immunodeficiency virus (SIV) do not develop SIV encephalitis (SIVE) and maintain low brain viral loads despite having similar plasma viral loads compared to SIV-infected adults. We hypothesize that differences in myeloid cell populations that are the known target of SIV and HIV in the brain contribute to the lack of neonatal susceptibility to lentivirus-induced encephalitis. Using immunohistochemistry and immunofluorescence microscopy, we examined the frontal cortices from uninfected and SIV-infected infant and adult macaques (n = 8/ea) as well as adults with SIVE (n = 4) to determine differences in myeloid cell populations. The number of CD206+ brain perivascular macrophages (PVMs) was significantly greater in uninfected infants than in uninfected adults and was markedly lower in SIV-infected infants while microglia numbers were unchanged across groups. CD206+ PVMs, which proliferate after infection in SIV-infected adults, did not undergo proliferation in infants. While virtually all CD206+ cells in adults are also CD163+, infants have a distinct CD206 single-positive population in addition to the double-positive population commonly seen in adults. Notably, we found that more than 60% of these unique CD206+CD163- PVMs in SIV-infected infants were positive for cleaved caspase-3, an indicator of apoptosis, and that nearly 100% of this subset were concomitantly positive for the necroptosis marker receptor-interacting protein kinase-3 (RIP3). These findings show that distinct subpopulations of PVMs found in infants undergo programmed cell death instead of proliferation following SIV infection, which may lead to the absence of PVM-dependent SIVE and the limited size of the virus reservoir in the infant brain.

中文翻译：

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猴免疫缺陷病毒感染后，新生猕猴脑中的血管周围巨噬细胞发生大量坏死。

我们之前表明，新生儿感染猴免疫缺陷病毒 (SIV) 的恒河猴不会发生 SIV 脑炎 (SIVE)，尽管与 SIV 感染的成年人相比，其血浆病毒载量相似，但仍保持较低的脑病毒载量。我们假设，作为大脑中 SIV 和 HIV 已知靶点的骨髓细胞群的差异导致新生儿对慢病毒引起的脑炎缺乏易感性。我们使用免疫组织化学和免疫荧光显微镜检查了未感染和 SIV 感染的婴儿和成年猕猴（n = 8/ea）以及 SIVE 成年猕猴（n = 4）的额叶皮质，以确定髓细胞群的差异。未感染婴儿的 CD206+ 脑血管周围巨噬细胞 (PVM) 的数量显着多于未感染的成人，并且在 SIV 感染的婴儿中明显较低，而小胶质细胞的数量在各组中没有变化。CD206+ PVMs 在感染 SIV 的成人感染后增殖，在婴儿中没有增殖。虽然成人中几乎所有的 CD206+ 细胞也是 CD163+，但除了成人常见的双阳性细胞群外，婴儿还具有独特的 CD206 单阳性细胞群。值得注意的是，我们发现 SIV 感染婴儿中这些独特的 CD206+CD163-PVM 中有超过 60% 的 cleaved caspase-3 呈阳性，这是一种细胞凋亡的指标，并且该亚组中近 100% 的细胞坏死性凋亡标志物同时呈阳性受体相互作用蛋白激酶-3 (RIP3)。