Effect of morphine and SIV on dendritic cell trafficking into the central nervous system of rhesus macaques.

Effect of morphine and SIV on dendritic cell trafficking into the central nervous system of rhesus macaques.
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DOI:
10.1007/s13365-013-0182-x
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发表时间:
2014-04
影响因子:
3.2
通讯作者:
Jain, Pooja
Jain, Pooja
中科院分区:
医学4区
文献类型:
--
作者:
Hollenbach, Rebecca;Sagar, Divya;Khan, Zafar K.;Callen, Shannon;Yao, Honghong;Shirazi, Jasmine;Buch, Shilpa;Jain, Pooja

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免疫细胞如单核细胞/巨噬细胞和树突状细胞(DC)跨越血脑屏障(BBB)的募集已经在涉及神经炎症的疾病中被记录。HIV的神经侵入导致神经认知疾病并改变BBB的通透性。同样,许多HIV患者使用滥用药物,如吗啡,这可能进一步损害BBB。虽然单核细胞和巨噬细胞在neuroAIDS中的作用已经得到了很好的确立,但证明DC在HIV感染期间在CNS中的存在和作用的研究尚未开发。在这方面,本研究探讨了在恒河猴的脑实质中存在的树突状细胞感染的神经毒性形式的SIV(SIV mac 239 R71/17 E),并与吗啡。在SIV感染的猕猴以及吗啡感染的猕猴的脑实质中一致地发现DC标志物阳性的细胞,包括CD 11 c(整合素)、macDC-SIGN(树突状细胞特异性ICAM-3抓取非整合素)、CD 83(成熟因子)和HLA-DR(MHC II类)。对照组动物的脑中未显示任何DC存在。这些结果提供了第一个证据,证明DCs与神经艾滋病维斯药物滥用的相关性,并开辟了理解和调查HIV-CNS伤害的新途径。
Recruitment of immune cells such as monocytes/macrophages and dendritic cells (DCs) across the blood-brain barrier (BBB) has been documented in diseases involving neuroinflammation. Neuroinvasion by HIV leads to neurocognitive diseases and alters the permeability of the BBB. Likewise, many HIV patients use drugs of abuse such as morphine, which can further compromise the BBB. While the role of monocytes and macrophages in neuroAIDS is well established, research demonstrating the presence and role of DCs in the CNS during HIV infection has not been developed yet. In this respect, this study explored the presence of DCs in the brain parenchyma of rhesus macaques infected with a neurovirulent form of SIV (SIV mac239 R71/17E) and administered with morphine. Cells positive for DC markers including CD11c (integrin), macDC-SIGN (dendritic cell-specific ICAM-3 grabbing nonintegrin), CD83 (a maturation factor) and HLA-DR (MHC class II) were consistently found in the brain parenchyma of SIV-infected macaques as well as infected macaques on morphine. Control animals did not exhibit any DC presence in their brains. These results provide first evidence of DCs’ relevance in NeuroAIDS vis-à-vis drugs of abuse and open new avenues of understanding and investigative HIV-CNS inflictions.
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