暂时解决的单细胞RNA测序揭示了单纯疱疹病毒CNS感染期间的保护性和病理反应。

IF 10.1 1区 医学 Q1 IMMUNOLOGY
Xiangning Ding, Xin Lai, Ida H Klaestrup, Sara R N Jensen, Morten M Nielsen, Kasper Thorsen, Marina Romero-Ramos, Yonglun Luo, Lin Lin, Line S Reinert, Søren R Paludan
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引用次数: 0

摘要

背景:单纯疱疹病毒1型(HSV-1)是一种致脑炎和感染后并发症的嗜神经病毒。感染可诱发一系列急性、亚急性和进展性脑疾病,近年来发现免疫反应参与了这些疾病的发病机制。方法:通过角膜感染感染HSV-1小鼠,利用单细胞和GeoMx空间转录组学对脑干进行分析。通过这些技术,我们分析了与抗病毒活性和炎症诱导的生理脑结构和活动紊乱相关的细胞群、途径和细胞间通讯的时间转录组变化。结果:我们发现HSV-1感染后小胶质细胞比例早期增加,随后单核细胞内流,随后T细胞内流。血脑屏障被破坏,与稳态脑转录活动相关的转录组谱被改变。早期的转录反应主要是抗病毒和炎症活性。在感染部位具有高I型干扰素和趋化因子表达的小胶质细胞亚群,可能介导抗病毒防御和免疫募集。单核细胞亚群表现出比小胶质细胞更广泛的激活谱,是免疫细胞间串扰的中心介质。来自小胶质细胞、单核细胞和T细胞的细胞因子重新编程了脑细胞,特别是内皮细胞和少突胶质细胞,破坏了大脑功能。比较来自各种脑部疾病的数据集,发现鉴定出的小胶质细胞亚群对病毒感染具有特异性。结论:本研究确定了一种独特的病毒激活小胶质细胞群,具有抗病毒和促炎特性,并揭示了单核细胞是病毒感染大脑中相互作用驱动病理的关键驱动因素。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Temporally resolved single-cell RNA sequencing reveals protective and pathological responses during herpes simplex virus CNS infection.

Background: Herpes Simplex Virus 1 (HSV-1) is a neurotropic virus causing encephalitis and post-infectious complications. Infections can induce a range of acute, subacute, and progressing brain disease, and in recent years it has emerged that immune responses are involved in the pathogenesis of these diseases.

Methods: Mice were infected with HSV-1 through corneal infection, and the brain stem was analyzed using single-cell and GeoMx spatial transcriptomics. Through these technologies we profiled temporal transcriptomic changes in cell populations, pathways, and cell-cell communication associated with antiviral activity and inflammation-induced disturbance of physiological brain structures and activities.

Results: We found that microglia proportions increased early after HSV-1 infection, followed by monocyte influx and later by T cells. The blood-brain barrier was disrupted, and transcriptomic profiles associated with homeostatic brain transcriptional activities were altered. Early transcriptional responses were dominated by antiviral and inflammatory activities. A microglia subpopulation with high type I interferon and chemokine expression localized to infection sites, likely mediating antiviral defense and immune recruitment. Monocyte subpopulations displayed a broader activation profile than microglia and was a central mediator of crosstalk between immune cells. Cytokines from microglia, monocytes, and T cells reprogrammed brain cells, notably endothelial cells and oligodendrocytes, disrupting brain functions. Comparing datasets from various brain diseases revealed the identified microglia subpopulation as specific to viral infections.

Conclusions: This study identifies a unique population of virus-activated microglia with antiviral and proinflammatory properties and reveals monocytes to be a key driver of interactions driving pathology in the virus-infected brain.

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来源期刊
Journal of Neuroinflammation
Journal of Neuroinflammation 医学-神经科学
CiteScore
15.90
自引率
3.20%
发文量
276
审稿时长
1 months
期刊介绍: The Journal of Neuroinflammation is a peer-reviewed, open access publication that emphasizes the interaction between the immune system, particularly the innate immune system, and the nervous system. It covers various aspects, including the involvement of CNS immune mediators like microglia and astrocytes, the cytokines and chemokines they produce, and the influence of peripheral neuro-immune interactions, T cells, monocytes, complement proteins, acute phase proteins, oxidative injury, and related molecular processes. Neuroinflammation is a rapidly expanding field that has significantly enhanced our knowledge of chronic neurological diseases. It attracts researchers from diverse disciplines such as pathology, biochemistry, molecular biology, genetics, clinical medicine, and epidemiology. Substantial contributions to this field have been made through studies involving populations, patients, postmortem tissues, animal models, and in vitro systems. The Journal of Neuroinflammation consolidates research that centers around common pathogenic processes. It serves as a platform for integrative reviews and commentaries in this field.
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