Single-Cell Analysis of Diverse Pathogen Responses Defines a Molecular Roadmap for Generating Antigen-Specific Immunity
Single-Cell Analysis of Diverse Pathogen Responses Defines a Molecular Roadmap for Generating Antigen-Specific Immunity
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DOI：
10.1016/j.cels.2019.01.001
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发表时间：
2019-02-27
期刊：
影响因子：
9.3
通讯作者：
Amit, Ido
中科院分区：
文献类型：
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作者：
Blecher-Gonen, Ronnie;Bost, Pierre;Amit, Ido
免疫系统产生针对病原体的反应。精确的先天性免疫细胞类型和途径，直接强大的适应性免疫反应尚未得到充分的表征。通过使用荧光病原体结合大规模平行单细胞RNA-seq，我们全面表征了对不同病原体的先天免疫应答的最初48小时。我们发现，在所有测试的病原体中，大多数淋巴结细胞类型和状态几乎没有病原体特异性。与此相反，罕见的抗原阳性细胞显示病原体特异性转录程序早在24小时后免疫。此外，分枝杆菌激活了一个特定的NK驱动的IFN γ反应。NK细胞和IFN γ的耗竭表明IFN γ启动单核细胞特异性信号级联，导致促进Th 1发育的主要趋化因子和细胞因子的产生。我们的系统免疫学方法揭示了先天免疫反应的早期事件，并可能有助于进一步开发安全有效的疫苗。
The immune system generates pathogen-tailored responses. The precise innate immune cell types and pathways that direct robust adaptive immune responses have not been fully characterized. By using fluorescent pathogens combined with massively parallel single-cell RNA-seq, we comprehensively characterized the initial 48 h of the innate immune response to diverse pathogens. We found that across all pathogens tested, most of the lymph node cell types and states showed little pathogen specificity. In contrast, the rare antigen-positive cells displayed pathogen-specific transcriptional programs as early as 24 h after immunization. In addition, mycobacteria activated a specific NK-driven IFN gamma response. Depletion of NK cells and IFN gamma showed that IFN gamma initiated a monocyte-specific signaling cascade, leading to the production of major chemokines and cytokines that promote Th1 development. Our systems immunology approach sheds light on early events in innate immune responses and may help further development of safe and efficient vaccines.