Department of Pathology, University of Veterinary Medicine Hannover, 30559, Hannover, Germany.
Center for Systems Neuroscience, 30559, Hannover, Germany.
Sci Rep. 2021 Dec 10;11(1):23819. doi: 10.1038/s41598-021-03201-2.
Neurotropic viruses target the brain and contribute to neurologic diseases. C-type lectin receptors (CLRs) are pattern recognition receptors that recognize carbohydrate structures on endogenous molecules and pathogens. The myeloid CLR dendritic cell immunoreceptor (DCIR) is expressed by antigen presenting cells and mediates inhibitory intracellular signalling. To investigate the effect of DCIR on neurotropic virus infection, mice were infected experimentally with Theiler's murine encephalomyelitis virus (TMEV). Brain tissue of TMEV-infected C57BL/6 mice and DCIR mice were analysed by histology, immunohistochemistry and RT-qPCR, and spleen tissue by flow cytometry. To determine the impact of DCIR deficiency on T cell responses upon TMEV infection in vitro, antigen presentation assays were utilised. Genetic DCIR ablation in C57BL/6 mice was associated with an ameliorated hippocampal integrity together with reduced cerebral cytokine responses and reduced TMEV loads in the brain. Additionally, absence of DCIR favoured increased peripheral cytotoxic CD8 T cell responses following TMEV infection. Co-culture experiments revealed that DCIR deficiency enhances the activation of antigen-specific CD8 T cells by virus-exposed dendritic cells (DCs), indicated by increased release of interleukin-2 and interferon-γ. Results suggest that DCIR deficiency has a supportive influence on antiviral immune mechanisms, facilitating virus control in the brain and ameliorates neuropathology during acute neurotropic virus infection.
神经亲和性病毒靶向大脑并导致神经疾病。C 型凝集素受体（CLRs）是一种模式识别受体，可识别内源性分子和病原体上的碳水化合物结构。髓样 CLR 树突状细胞免疫受体（DCIR）由抗原呈递细胞表达，并介导抑制性细胞内信号转导。为了研究 DCIR 对神经亲和性病毒感染的影响，实验性地用 Theiler 氏鼠脑脊髓炎病毒（TMEV）感染了小鼠。通过组织学、免疫组织化学和 RT-qPCR 分析 TMEV 感染的 C57BL/6 小鼠和 DCIR 小鼠的脑组织，并通过流式细胞术分析脾脏组织。为了确定 DCIR 缺陷对 TMEV 感染后体外 T 细胞反应的影响，利用了抗原呈递测定法。C57BL/6 小鼠中 DCIR 的基因缺失与海马体完整性的改善有关，伴有脑内细胞因子反应降低和 TMEV 载量降低。此外，DCIR 缺失有利于 TMEV 感染后外周细胞毒性 CD8 T 细胞反应的增加。共培养实验表明，DCIR 缺陷增强了暴露于病毒的树突状细胞（DC）对抗原特异性 CD8 T 细胞的激活，这表现为白细胞介素-2 和干扰素-γ的释放增加。结果表明，DCIR 缺失对抗病毒免疫机制具有支持作用，有利于控制大脑中的病毒并改善急性神经亲和性病毒感染期间的神经病理学。
