Single-Cell RNA Sequencing Reveals the Diversity of the Immunological Landscape following Central Nervous System Infection by a Murine Coronavirus.
Single-Cell RNA Sequencing Reveals the Diversity of the Immunological Landscape following Central Nervous System Infection by a Murine Coronavirus.
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DOI：
10.1128/jvi.01295-20
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发表时间：
2020-11-23
影响因子：
5.4
通讯作者：
Lane TE
中科院分区：
文献类型：
--
作者：
Syage AR;Ekiz HA;Skinner DD;Stone C;O'Connell RM;Lane TE
鉴于越来越多的病毒能够在神经系统内感染和复制，了解CNS病毒感染后宿主防御和疾病的免疫机制至关重要。考虑到这一点，本研究旨在使用scRNAseq在感染神经适应性鼠冠状病毒后的规定时间评估CNS内免疫细胞的分子特征。这种方法揭示了免疫学景观是多样的，许多免疫细胞亚群表达不同的mRNA表达谱，这部分取决于感染的阶段。此外，这些发现揭示了对有助于控制病毒复制以及神经系统疾病的细胞途径的新见解。颅内（i.c.）用小鼠肝炎病毒（JHMV）的嗜神经性JHM株（冠状病毒科的一个成员）感染易感的C57 BL/6小鼠导致急性脑脊髓炎和与免疫介导的脱髓鞘疾病相关的病毒持续存在。本研究旨在更好地了解先天性和适应性免疫应答以及中枢神经系统（CNS）JHMV感染引起的慢性脱髓鞘疾病阶段引起的分子途径。使用单细胞RNA测序分析（scRNAseq）的流式分选的CD 45阳性（CD 45+）细胞富集从实验小鼠的大脑和脊髓，我们证明了免疫反应的异质性所确定的独特的分子特征和参与有效的抗病毒宿主防御的途径的存在。此外，我们确定了参与脱髓鞘以及由小胶质细胞和巨噬细胞表达的髓鞘再生的潜在基因。总的来说，这些发现强调了病毒感染中枢神经系统后特定阶段免疫反应和分子网络的多样性。重要性鉴于越来越多的病毒能够在神经系统内感染和复制，了解CNS病毒感染后促进宿主防御和疾病的免疫机制至关重要。考虑到这一点，本研究旨在使用scRNAseq在感染神经适应性鼠冠状病毒后的规定时间评估CNS内免疫细胞的分子特征。这种方法揭示了免疫学景观是多样的，许多免疫细胞亚群表达不同的mRNA表达谱，这部分取决于感染的阶段。此外，这些发现揭示了对有助于控制病毒复制以及神经系统疾病的细胞途径的新见解。
Understanding the immunological mechanisms contributing to both host defense and disease following viral infection of the CNS is of critical importance given the increasing number of viruses that are capable of infecting and replicating within the nervous system. With this in mind, the present study was undertaken to evaluate the molecular signatures of immune cells within the CNS at defined times following infection with a neuroadapted murine coronavirus using scRNAseq. This approach has revealed that the immunological landscape is diverse, with numerous immune cell subsets expressing distinct mRNA expression profiles that are, in part, dictated by the stage of infection. In addition, these findings reveal new insight into cellular pathways contributing to control of viral replication as well as to neurologic disease. Intracranial (i.c.) infection of susceptible C57BL/6 mice with the neurotropic JHM strain of mouse hepatitis virus (JHMV) (a member of the Coronaviridae family) results in acute encephalomyelitis and viral persistence associated with an immune-mediated demyelinating disease. The present study was undertaken to better understand the molecular pathways evoked during innate and adaptive immune responses as well as the chronic demyelinating stage of disease in response to JHMV infection of the central nervous system (CNS). Using single-cell RNA sequencing analysis (scRNAseq) on flow-sorted CD45-positive (CD45+) cells enriched from brains and spinal cords of experimental mice, we demonstrate the heterogeneity of the immune response as determined by the presence of unique molecular signatures and pathways involved in effective antiviral host defense. Furthermore, we identify potential genes involved in contributing to demyelination as well as remyelination being expressed by both microglia and macrophages. Collectively, these findings emphasize the diversity of the immune responses and molecular networks at defined stages following viral infection of the CNS. IMPORTANCE Understanding the immunological mechanisms contributing to both host defense and disease following viral infection of the CNS is of critical importance given the increasing number of viruses that are capable of infecting and replicating within the nervous system. With this in mind, the present study was undertaken to evaluate the molecular signatures of immune cells within the CNS at defined times following infection with a neuroadapted murine coronavirus using scRNAseq. This approach has revealed that the immunological landscape is diverse, with numerous immune cell subsets expressing distinct mRNA expression profiles that are, in part, dictated by the stage of infection. In addition, these findings reveal new insight into cellular pathways contributing to control of viral replication as well as to neurologic disease.
影响因子：
4.3
作者：
Marro BS;Blanc CA;Loring JF;Cahalan MD;Lane TE
通讯作者：
Lane TE