Department of Medicine, Section of Infectious Diseases.
Department of Neurology.
JCI Insight. 2018 Sep 20;3(18). doi: 10.1172/jci.insight.121718.
Central nervous system (CNS) immune activation is an important driver of neuronal injury during several neurodegenerative and neuroinflammatory diseases. During HIV infection, CNS immune activation is associated with high rates of neurocognitive impairment, even during sustained long-term suppressive antiretroviral therapy (ART). However, the cellular subsets that drive immune activation and neuronal damage in the CNS during HIV infection and other neurological conditions remain unknown, in part because CNS cells are difficult to access in living humans. Using single-cell RNA sequencing (scRNA-seq) on cerebrospinal fluid (CSF) and blood from adults with and without HIV, we identified a rare (<5% of cells) subset of myeloid cells that are found only in CSF and that present a gene expression signature that overlaps significantly with neurodegenerative disease-associated microglia. This highlights the power of scRNA-seq of CSF to identify rare CNS immune cell subsets that may perpetuate neuronal injury during HIV infection and other conditions.
中枢神经系统（CNS）免疫激活是几种神经退行性和神经炎症性疾病中神经元损伤的重要驱动因素。在 HIV 感染期间，CNS 免疫激活与高比例的神经认知障碍相关，即使在持续的长期抑制性抗逆转录病毒治疗（ART）期间也是如此。然而，在 HIV 感染和其他神经疾病期间驱动 CNS 免疫激活和神经元损伤的细胞亚群仍不清楚，部分原因是中枢神经系统细胞在活体人类中难以获取。我们使用来自 HIV 感染者和非感染者的脑脊液（CSF）和血液的单细胞 RNA 测序（scRNA-seq），鉴定了一种罕见的（<5%的细胞）髓样细胞亚群，该亚群仅存在于 CSF 中，其基因表达特征与神经退行性疾病相关的小胶质细胞显著重叠。这突显了 CSF 的 scRNA-seq 用于识别可能在 HIV 感染和其他情况下持续导致神经元损伤的罕见 CNS 免疫细胞亚群的强大功能。
