Single-cell landscape of peripheral immune responses to fatal SFTS

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 in SFTS exacerbation remains unclear. Here we show the single-cell landscape of peripheral immune responses is reprogrammed in SFTS and characterized by monocyte shift to intermediate type along with complement activation, perturbation of plasmablasts composition, and highly exhausted T cells, all are correlated with lethal consequences. We identify the overexpression of interferon-stimulated genes across most immune cell types post SFTSV infection, which are simultaneously related to older age, high viremia and hyper-inflammation response. A retrospectively clinical study revealed 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 SFTSV infection, and propose the pivotal role of IFN-I response in exacerbating hyper-inflammation and lethal SFTS.

严重发热伴血小板减少综合征（SFTS）是一种致死率较高的新兴传染病。SFTS的预后不良与宿主免疫失调有关，然而，与SFTS病情恶化相关的病理生理学免疫模式尚不明确。本研究揭示了SFTS中单细胞免疫反应图谱的重编程，其特征为单核细胞向中间型转变，伴随补体激活、浆细胞生成组成紊乱以及高度耗竭的T细胞，这些均与致命后果密切相关。我们鉴定出SFTSV感染后大多数免疫细胞类型中干扰素刺激基因的过度表达，这些基因同时与高龄、高病毒血症和过度炎症反应相关。回顾性临床研究表明，IFN-α在治疗SFTS方面无效。这些数据共同支持中间型单核细胞和IFN-I诱导的浆细胞生成是SFTSV感染的主要靶点，并提出IFN-I反应在加剧过度炎症和致命SFTS中的关键作用。