Michigan State University, East Lansing, MI, USA.
Cell & Molecular Biology Program, Michigan State University, East Lansing, MI, USA.
J Neuroimmune Pharmacol. 2020 Dec;15(4):780-793. doi: 10.1007/s11481-020-09918-7. Epub 2020 May 14.
HIV infection affects an estimated 38 million people. Approximately 50% of HIV patients exhibit neurocognitive dysfunction termed HIV-Associated Neurocognitive Disorder (HAND). HAND is a consequence of chronic low-level neuroinflammation due to HIV entry into the brain. Initially, monocytes become activated in circulation and traffic to the brain. Monocytes, when activated, become susceptible to infection by HIV and can then carry the virus across the blood brain barrier. Once in the brain, activated monocytes secrete chemokines, which recruit virus-specific CD8 T cells into the brain to further promote neuroinflammation. HAND is closely linked to systemic inflammation driven, in part, by HIV but is also due to persistent translocation of microorganisms across the GI tract. Persistent anti-viral responses in the GI tract compromise microbial barrier integrity. Indeed, HIV patients can exhibit remarkably high levels of activated (CD16) monocytes in circulation. Recent studies, including our own, show that HIV patients using medical marijuana exhibit lower levels of circulating CD16 monocytes than non-cannabis using HIV patients. Cannabis is a known immune modulator, including anti-inflammatory properties, mediated, in part, by ∆-tetrahydrocannabinol (THC), as well as less characterized minor cannabinoids, such as cannabidiol (CBD), terpenes and presumably other cannabis constituents. The immune modulating activity of THC is largely mediated through cannabinoid receptors (CB) 1 and 2, with CB1 also responsible for the psychotropic properties of cannabis. Here we discuss the anti-inflammatory properties of cannabinoids in the context of HIV and propose CB2 as a putative therapeutic target for the treatment of neuroinflammation. Graphical Abstract HIV-associated neurocognitive disorder is a systemic inflammatory disease leading to activation of plasmacytoid dendritic cells, monocytes and T cells. Monocyte and CD8 T cell migration across the BBB and interaction with astrocytes promotes neurotoxic inflammatory mediators release. CB2 ligands are proposed as therapeutics capable of suppressing systemic and localized inflammation.
HIV 感染影响了约 3800 万人。大约 50%的 HIV 患者表现出神经认知功能障碍，称为 HIV 相关神经认知障碍 (HAND)。HAND 是由于 HIV 进入大脑引起的慢性低度神经炎症的结果。最初，单核细胞在循环中被激活并转移到大脑。单核细胞被激活后，容易被 HIV 感染，然后可以携带病毒穿过血脑屏障。一旦进入大脑，激活的单核细胞就会分泌趋化因子，招募病毒特异性 CD8 T 细胞进入大脑，进一步促进神经炎症。HAND 与系统炎症密切相关，部分原因是 HIV，但也与微生物通过胃肠道持续易位有关。胃肠道中持续的抗病毒反应损害了微生物屏障的完整性。事实上，HIV 患者的循环中可以表现出非常高水平的活化 (CD16) 单核细胞。最近的研究，包括我们自己的研究，表明使用医用大麻的 HIV 患者的循环 CD16 单核细胞水平低于不使用大麻的 HIV 患者。大麻是一种已知的免疫调节剂，包括抗炎特性，部分由 ∆-四氢大麻酚 (THC) 介导，以及不太典型的次要大麻素，如大麻二酚 (CBD)、萜烯和可能的其他大麻成分。THC 的免疫调节活性主要通过大麻素受体 (CB)1 和 2 介导，CB1 还负责大麻的精神活性特性。在这里，我们讨论了大麻素在 HIV 中的抗炎特性，并提出 CB2 作为治疗神经炎症的潜在治疗靶点。
