Single-cell temporal analysis of natural dengue infection reveals skin-homing lymphocyte expansion one day before defervescence.
Single-cell temporal analysis of natural dengue infection reveals skin-homing lymphocyte expansion one day before defervescence.
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DOI：
10.1016/j.isci.2022.104034
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发表时间：
2022-04-15
期刊：
影响因子：
5.8
通讯作者：
Charoensawan V
中科院分区：
文献类型：
--
作者：
Arora JK;Opasawatchai A;Poonpanichakul T;Jiravejchakul N;Sungnak W;DENFREE Thailand;Matangkasombut O;Teichmann SA;Matangkasombut P;Charoensawan V
急性登革病毒（DENV）感染的有效临床管理依赖于疾病进展期间适当治疗的时机。我们分析了来自两名DENV患者的外周血单核细胞样本的单细胞转录组学谱，这些样本在急性期和恢复期每天收集。关键的免疫细胞类型在感染过程中表现出不同的动态反应。在退热前一天（第-1天），我们观察到适应性免疫途径中几个突出基因的表达峰值。我们还表征了在第-1天表达皮肤归巢特征基因的独特效应T细胞簇，而在发热期间在浆细胞和浆母细胞中也观察到皮肤和肠道归巢基因的上调。这项工作提供了一个独特的分子动力学的概述，标志着进入关键阶段，这些发现可以改善登革病毒感染的患者管理。时间进程scRNA-seq揭示了急性登革热感染期间的免疫应答动力学在发热消退前一天（第-1天）观察到快速转录转换在发热期期间在特异性T细胞中观察到皮肤归巢特征在第-1天皮肤归巢CD 69 + PD-1+ T细胞的扩增用FACS证实单细胞组学;系统生物学;免疫学
Effective clinical management of acute dengue virus (DENV) infection relies on the timing of suitable treatments during the disease progression. We analyzed single-cell transcriptomic profiles of the peripheral blood mononuclear cell samples from two DENV patients, collected daily during acute phase and also at convalescence. Key immune cell types demonstrated different dynamic responses over the course of the infection. On the day before defervescence (Day −1), we observed the peak expression of several prominent genes in the adaptive immunological pathways. We also characterized unique effector T cell clusters that expressed skin-homing signature genes at Day −1, whereas upregulation of skin and gut homing genes was also observed in plasma cells and plasmablasts during the febrile period. This work provides an overview of unique molecular dynamics that signify the entry of the critical phase, and the findings could improve the patient management of DENV infection. Time-course scRNA-seq reveals immune response dynamics during acute dengue infection Rapid transcriptional switching was observed one day before fever subsided (Day -1) Skin-homing signatures were observed in specific T cells during the febrile phase Expansion of skin-homing CD69+ PD-1+ T cells at Day -1 was confirmed with FACS Single-cell Omics; Systems biology; Immunology
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