Longitudinal Study of Cellular and Systemic Cytokine Signatures to Define the Dynamics of a Balanced Immune Environment During Disease Manifestation in Zika Virus-Infected Patients.

Longitudinal Study of Cellular and Systemic Cytokine Signatures to Define the Dynamics of a Balanced Immune Environment During Disease Manifestation in Zika Virus-Infected Patients.
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DOI:
10.1093/infdis/jiy225
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发表时间:
2018-07-24
期刊:
The Journal of infectious diseases
影响因子:
--
通讯作者:
Ng LFP
Ng LFP
中科院分区:
其他
文献类型:
--
作者:
Lum FM;Lye DCB;Tan JJL;Lee B;Chia PY;Chua TK;Amrun SN;Kam YW;Yee WX;Ling WP;Lim VWX;Pang VJX;Lee LK;Mok EWH;Chong CY;Leo YS;Ng LFP

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了解寨卡病毒(ZIKV)感染期间的宿主免疫反应将为ZIKV免疫发病机制提供有价值的见解。在这项研究中,对ZIKV感染患者的细胞变化和免疫介质进行了表征,从而可以识别关键的感染相关标志物。寨卡病毒(ZIKV)在全球范围内引起了多次疫情。本研究表征了ZIKV感染期间的宿主免疫应答。在2016年末新加坡爆发期间,在ZIKV感染的急性期、恢复期和恢复期的6个月内纵向收集患者样品。血浆免疫介质通过多重微珠分析,而血细胞数量的变化与免疫表型测定。数据显示,在急性ZIKV感染期间,各种免疫介质的参与伴随着除了CD14+单核细胞之外的所有免疫亚群的血细胞数量的普遍减少。重要的是,出现中度症状的病毒血症患者的干扰素γ诱导蛋白10、单核细胞趋化蛋白1、白细胞介素1受体拮抗剂、白细胞介素8和胎盘生长因子1的数量显著较高,伴有外周血CD8+ T细胞、CD4+ T细胞和双阴性T细胞数量减少。包括干扰素γ诱导蛋白10、干扰素γ和白细胞介素10在内的T细胞相关介质的水平在ZIKV感染的恢复期较高,表明T细胞的功能作用。在特定疾病阶段鉴定不同的标志物强调了疾病进展中平衡的细胞因子环境的动态。这是第一项全面的研究,突出了ZIKV疾病进展期间的特定细胞变化和免疫特征,并为ZIKV免疫发病机制提供了有价值的见解。
Understanding the host immune response during Zika virus (ZIKV) infection will provide valuable insights into ZIKV immunopathogenesis. In this study, characterization of cellular changes and immune mediators of ZIKV-infected patients was performed, allowing for the identification of key infection-associated markers. Since its unexpected reemergence, Zika virus (ZIKV) has caused numerous outbreaks globally. This study characterized the host immune responses during ZIKV infection. Patient samples were collected longitudinally during the acute, convalescence and recovery phases of ZIKV infection over 6 months during the Singapore outbreak in late 2016. Plasma immune mediators were profiled via multiplex microbead assay, while changes in blood cell numbers were determined with immunophenotyping. Data showed the involvement of various immune mediators during acute ZIKV infection accompanied by a general reduction in blood cell numbers for all immune subsets except CD14+ monocytes. Importantly, viremic patients experiencing moderate symptoms had significantly higher quantities of interferon γ–induced protein 10, monocyte chemotactic protein 1, interleukin 1 receptor antagonist, interleukin 8, and placental growth factor 1, accompanied by reduced numbers of peripheral CD8+ T cells, CD4+ T cells, and double-negative T cells. Levels of T-cell associated mediators, including interferon γ–induced protein 10, interferon γ, and interleukin 10, were high in recovery phases of ZIKV infection, suggesting a functional role for T cells. The identification of different markers at specific disease phases emphasizes the dynamics of a balanced cytokine environment in disease progression. This is the first comprehensive study that highlights specific cellular changes and immune signatures during ZIKV disease progression, and it provides valuable insights into ZIKV immunopathogenesis.
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