Vitalant Research Institute, San Francisco, CA, United States.
Department of Laboratory Medicine, University of California, San Francisco, CA, United States.
Front Immunol. 2022 Dec 19;13:1033712. doi: 10.3389/fimmu.2022.1033712. eCollection 2022.
Neurocognitive impairment remains prevalent in people with HIV (PWH) despite long term virological suppression by antiretroviral therapy (ART) regimens. Systemic and neuro-inflammatory processes are suggested to contribute to the complex pathology leading to cognitive impairment in this population, yet the underlying mechanisms remain unresolved. Extracellular vesicles (EVs) play a central role in intracellular communication and have emerged as key modulators of immunological and inflammatory responses. In this report, we examined the impact of EVs in PWH experiencing cognitive deficits to determine their relevance in HIV associated neuropathology.
EV phenotypes were measured in plasma samples from 108 PWH with either cognitive impairment (CI, n=92) or normal cognition (NC, n=16) by flow cytometry. Matched cerebrospinal fluid (CSF)-derived EVs were similarly profiled from a subgroup of 84 individuals who underwent a lumbar puncture. Peripheral blood mononuclear cells were assayed by flow cytometry to measure monocyte frequencies in a subset of 32 individuals.
Plasma-EVs expressing CD14, CD16, CD192, C195, and GFAP were significantly higher in HIV-infected individuals with cognitive impairment compared to individuals with normal cognition. Increased CSF-EVs expressing GFAP and CD200 were found in the cognitive impairment group compared to the normal cognition group. Frequencies of patrolling monocytes correlated with plasma-EVs expressing CD14, CD66b, MCSF, MAP2, and GFAP. Frequencies of CD195 expression on monocytes correlated positively with plasma-EVs expressing CD41a, CD62P, and CD63. Expression of CD163 on monocytes correlated positively with CSF-EVs expressing GFAP and CD200. Finally, the expression of CD192 on total monocytes correlated with CSF-EVs expressing CD200, CD62P, and CD63.
EVs expressing monocyte activation and neuronal markers associated with HIV associated cognitive impairment, suggesting that distinct EV subsets may serve as novel biomarkers of neuronal injury in HIV infection. Further circulating platelet EV levels were linked to monocyte activation indicating a potential novel interaction in the pathogenesis of HIV-related cognitive impairment.
尽管抗逆转录病毒疗法（ART）方案可长期抑制病毒，但 HIV 感染者（PWH）仍存在神经认知障碍。有研究表明，全身和神经炎症过程有助于导致该人群认知障碍的复杂病理，但潜在机制仍未解决。细胞外囊泡（EVs）在细胞内通讯中发挥核心作用，并已成为免疫和炎症反应的关键调节剂。在本报告中，我们研究了 EVs 在认知功能障碍的 PWH 中的作用，以确定它们与 HIV 相关神经病理学的相关性。
通过流式细胞术测量了 108 名 HIV 感染者（92 名认知障碍（CI）和 16 名认知正常（NC））血浆样本中的 EV 表型。从接受腰椎穿刺的 84 名个体中类似地对脑脊液（CSF）衍生的 EVs 进行了分析。通过流式细胞术对部分 32 名个体的外周血单核细胞进行了检测，以测量单核细胞频率。
与认知正常的个体相比，认知障碍的 HIV 感染者血浆 EV 表达 CD14、CD16、CD192、C195 和 GFAP 明显更高。与认知正常组相比，认知障碍组 CSF-EVs 表达 GFAP 和 CD200 增加。巡逻单核细胞的频率与血浆 EV 表达 CD14、CD66b、MCSF、MAP2 和 GFAP 相关。单核细胞 CD195 表达与单核细胞 CD41a、CD62P 和 CD63 表达的血浆 EV 呈正相关。单核细胞 CD163 表达与 CSF-EVs 表达 GFAP 和 CD200 呈正相关。最后，总单核细胞 CD192 表达与 CSF-EVs 表达 CD200、CD62P 和 CD63 相关。
表达与 HIV 相关认知障碍相关的单核细胞激活和神经元标志物的 EVs 表明，不同的 EV 亚群可能作为 HIV 感染中神经元损伤的新型生物标志物。此外，循环血小板 EV 水平与单核细胞激活相关，表明 HIV 相关认知障碍发病机制中存在潜在的新的相互作用。
