Recent findings have highlighted the role of microglia in orchestrating normal development and refining neural network connectivity in the healthy CNS. Microglia are not only vital cells in maintaining CNS homeostasis, but also respond to injury, infection, and disease by undergoing proliferation and changes in transcription and morphology. A better understanding of the specific role of microglia in responding to viral infection is complicated by the presence of nonmicroglial myeloid cells with potentially overlapping function in the healthy brain and by the rapid infiltration of hematopoietic myeloid cells into the brain in diseased states. Here, we used an inhibitor of colony-stimulating factor 1 receptor (CSF1R) that depletes microglia to examine the specific roles of microglia in response to infection with the mouse hepatitis virus (MHV), a neurotropic coronavirus. Our results show that microglia were required during the early days after infection to limit MHV replication and subsequent morbidity and lethality. Additionally, microglia depletion resulted in ineffective T cell responses. These results reveal nonredundant, critical roles for microglia in the early innate and virus-specific T cell responses and for subsequent host protection from viral encephalitis.

中文翻译：

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小胶质细胞对预防小鼠致命的冠状病毒性脑炎是必需的

最近的发现强调了小胶质细胞在协调正常CNS中正常发育和改善神经网络连通性中的作用。小胶质细胞不仅是维持中枢神经系统稳态的重要细胞，而且还通过经历增殖以及转录和形态变化来响应损伤，感染和疾病。对小胶质细胞在应对病毒感染中的特定作用的更好的理解是，在健康的大脑中存在具有潜在重叠功能的非小胶质细胞，并且在患病状态下，造血性骨髓细胞会迅速渗透到大脑中。在这里，我们使用了抑制小胶质细胞的集落刺激因子1受体（CSF1R）抑制剂来研究小胶质细胞对小鼠肝炎病毒（MHV）感染的特定作用，嗜神经性冠状病毒。我们的结果表明，感染后的早期需要小胶质细胞来限制MHV复制以及随后的发病率和致死率。此外，小胶质细胞耗竭导致无效的T细胞反应。这些结果揭示了小胶质细胞在早期先天性和病毒特异性T细胞反应以及随后的宿主免受病毒性脑炎的保护中的非冗余关键作用。