Beijing Institute of Microbiology and Epidemiology, State Key Laboratory of Pathogen and Biosecurity, Beijing 100071, P.R. China; Graduate School of Anhui Medical University, Hefei 230022, P.R. China.
Beijing Institute of Microbiology and Epidemiology, State Key Laboratory of Pathogen and Biosecurity, Beijing 100071, P.R. China.
Cell Rep. 2021 Nov 23;37(8):110039. doi: 10.1016/j.celrep.2021.110039.
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-α 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.
严重发热伴血小板减少综合征（SFTS）是一种具有高病死率的新发传染病。SFTS 的预后不良与宿主免疫失调有关；然而，与 SFTS 加重相关的病理生理学相关的免疫模式仍不清楚。在这里，我们表明 SFTS 外周免疫反应的单细胞景观被重新编程，其特征是单核细胞向中间型转变，同时伴有补体激活、浆母细胞组成的扰动和高度耗竭的 T 细胞，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的干扰素（IFN）刺激基因表达过度，这与年龄较大、病毒载量较高和过度炎症反应同时相关。一项回顾性临床研究表明 IFN-α 治疗 SFTS 无效。这些数据共同支持中间型单核细胞和 IFN-I 诱导的浆母细胞是 SFTS 病毒感染的主要靶标，并表明 IFN-I 反应在加重过度炎症和致命性 SFTS 中的关键作用。
