Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Department of Neuroscience, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
J Neuroinflammation. 2024 Nov 5;21(1):288. doi: 10.1186/s12974-024-03275-5.
Neural stem cells have intact innate immune responses that protect them from virus infection and cell death. Yet, viruses can antagonize such responses to establish neuropathogenesis. Using a forebrain organoid model system at two developmental time points, we identified that neural stem cells, in particular radial glia, are basally primed to respond to virus infection by upregulating several antiviral interferon-stimulated genes. Infection of these organoids with a neuropathogenic Enterovirus-D68 strain, demonstrated the ability of this virus to impede immune activation by blocking interferon responses. Together, our data highlight immune gene signatures present in different types of neural stem cells and differential viral capacity to block neural-specific immune induction.
神经干细胞具有完整的先天免疫反应，可以保护它们免受病毒感染和细胞死亡。然而，病毒可以拮抗这种反应，从而建立神经发病机制。使用两个发育时间点的大脑器官样体模型系统，我们发现神经干细胞，特别是放射状胶质细胞，通过上调几种抗病毒干扰素刺激基因，基础地被预先激活以响应病毒感染。用神经致病性肠道病毒 D68 株感染这些器官样体，证明了这种病毒通过阻断干扰素反应来阻碍免疫激活的能力。总之，我们的数据突出了不同类型的神经干细胞中存在的免疫基因特征，以及病毒阻断神经特异性免疫诱导的不同能力。
