Single-cell landscape of peripheral immune responses to fatal SFTS
Single-cell landscape of peripheral immune responses to fatal SFTS
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DOI：
10.1016/j.celrep.2021.110039
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发表时间：
2021-11-23
期刊：
影响因子：
8.8
通讯作者：
Liu, Wei
中科院分区：
文献类型：
--
作者：
Li, Hao;Li, Xiaokun;Liu, Wei
严重发热伴血小板减少综合征（SFTS）是一种新发传染病，死亡率很高。 SFTS 的不良预后与宿主免疫失调有关；然而，与涉及 SFTS 恶化的病理生理学相关的免疫模式仍不清楚。在这里，我们发现外周免疫反应的单细胞景观在 SFTS 中被重新编程，其特征是单核细胞转变为中间类型，同时补体激活、浆母细胞组成扰动和 T 细胞高度耗尽，所有这些都与致命后果相关。我们发现，SFTSV 感染后，大多数免疫细胞类型中干扰素 (IFN) 刺激的基因过度表达，这些基因同时与老年、高病毒血症和高炎症反应相关。一项回顾性临床研究表明 IFN-a 治疗 SFTS 没有效果。这些数据共同支持中间单核细胞和 IFN-I 诱导性浆母细胞是 SFTS 病毒感染的主要目标，并且它们表明 IFN-I 反应在加剧过度炎症和致命 SFTS 中的关键作用。
Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with high fatality. Poor prognosis of SFTS has been associated with dysregulated host immunity; however, the immune patterns associated with pathophysiology involving SFTS exacerbation remain unclear. Here, we show that the single-cell landscape of peripheral immune responses is reprogrammed in SFTS and characterized by monocyte shift to an intermediate type along with complement activation, perturbation of plasmablast composition, and highly exhausted T cells, all correlated with lethal consequences. We identify the overexpression of interferon (IFN)-stimulated genes across most immune cell types after SFTSV infection, which are simultaneously related to older age, high viremia, and a hyperinflammatory response. A retrospective clinical study reveals no efficiency of IFN-a in treating SFTS. These data collectively support the intermediate monocytes and IFN-I-inducible plasmablasts to be major targets for SFTS virus infection, and they indicate the pivotal role of the IFN-I response in exacerbating hyperinflammation and lethal SFTS.