Virus-specific and shared gene expression signatures in immune cells after vaccination in response to influenza and vaccinia stimulation.
Virus-specific and shared gene expression signatures in immune cells after vaccination in response to influenza and vaccinia stimulation.
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DOI：
10.3389/fimmu.2023.1168784
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发表时间：
2023
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
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作者：
在疫苗时代，个人一生中会接种多种疫苗。响应于抗原刺激的宿主基因表达通常是病毒特异性的;然而，在广泛的疫苗病原体中鉴定宿主应答的共享途径可以阐明可以靶向用于开发广泛/通用治疗剂和疫苗的分子机制/组分。我们从接受季节性流感疫苗（<1年内）和天花疫苗（1 - 4年内）的健康供体的外周血中分离PBMC、单核细胞、B细胞和CD 8 + T细胞。用流感病毒或牛痘病毒刺激每个纯化的细胞群。对于每种体外病毒感染以及两种病毒感染（共享DEG），鉴定了相对于未刺激对照的差异表达基因（DEG）。进行途径富集分析以将鉴定的DEG与KEGG/生物途径相关联。我们在PBMC、单核细胞、B细胞和CD 8 + T细胞中分别鉴定了2，906、3，888、681和446个响应流感刺激的DEG。同时，在牛痘刺激后，分别在PBMC、单核细胞、B细胞和CD 8 + T细胞中鉴定出97、120、20和10个DEG作为基因标记。在任一病毒刺激后，在PBMC中鉴定的大多数DEG也在单核细胞中发现。在病毒特异性DEG中，55、63和9个DEG分别在PBMC、单核细胞和B细胞中常见，而在流感和牛痘后感染的CD 8 + T细胞中没有DEG共享。基因集富集分析表明，这些共享的DEG在先天性信号传导途径中过度表达，包括腺嘌呤-细胞因子受体相互作用、病毒蛋白与细胞因子和细胞因子受体的相互作用、Toll样受体信号传导、RIG-I样受体信号传导途径、胞质DNA传感途径和自然杀伤细胞介导的细胞毒性。我们的研究结果为不同免疫细胞中病毒与宿主的相互作用以及宿主对病毒刺激的防御机制提供了见解。我们的数据还强调了单核细胞作为主要细胞群体驱动离体PBMC中响应病毒刺激的基因表达的作用。本研究中确定的免疫应答信号通路可能为开发新的病毒特异性治疗剂和改进的牛痘和流感疫苗提供特定靶点。虽然流感病毒和牛痘病毒在本研究中已被选为病原体模型，这种方法可以适用于其他病原体。
In the vaccine era, individuals receive multiple vaccines in their lifetime. Host gene expression in response to antigenic stimulation is usually virus-specific; however, identifying shared pathways of host response across a wide spectrum of vaccine pathogens can shed light on the molecular mechanisms/components which can be targeted for the development of broad/universal therapeutics and vaccines. We isolated PBMCs, monocytes, B cells, and CD8+ T cells from the peripheral blood of healthy donors, who received both seasonal influenza vaccine (within <1 year) and smallpox vaccine (within 1 - 4 years). Each of the purified cell populations was stimulated with either influenza virus or vaccinia virus. Differentially expressed genes (DEGs) relative to unstimulated controls were identified for each in vitro viral infection, as well as for both viral infections (shared DEGs). Pathway enrichment analysis was performed to associate identified DEGs with KEGG/biological pathways. We identified 2,906, 3,888, 681, and 446 DEGs in PBMCs, monocytes, B cells, and CD8+ T cells, respectively, in response to influenza stimulation. Meanwhile, 97, 120, 20, and 10 DEGs were identified as gene signatures in PBMCs, monocytes, B cells, and CD8+ T cells, respectively, upon vaccinia stimulation. The majority of DEGs identified in PBMCs were also found in monocytes after either viral stimulation. Of the virus-specific DEGs, 55, 63, and 9 DEGs occurred in common in PBMCs, monocytes, and B cells, respectively, while no DEGs were shared in infected CD8+ T cells after influenza and vaccinia. Gene set enrichment analysis demonstrated that these shared DEGs were over-represented in innate signaling pathways, including cytokine-cytokine receptor interaction, viral protein interaction with cytokine and cytokine receptor, Toll-like receptor signaling, RIG-I-like receptor signaling pathways, cytosolic DNA-sensing pathways, and natural killer cell mediated cytotoxicity. Our results provide insights into virus-host interactions in different immune cells, as well as host defense mechanisms against viral stimulation. Our data also highlights the role of monocytes as a major cell population driving gene expression in ex vivo PBMCs in response to viral stimulation. The immune response signaling pathways identified in this study may provide specific targets for the development of novel virus-specific therapeutics and improved vaccines for vaccinia and influenza. Although influenza and vaccinia viruses have been selected in this study as pathogen models, this approach could be applicable to other pathogens.
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影响因子：
4.6
作者：
Voigt EA;Grill DE;Zimmermann MT;Simon WL;Ovsyannikova IG;Kennedy RB;Poland GA
通讯作者：
Poland GA
宿主基因表达签名区分了被遗传上相似H1N1菌株感染的雪貂。
影响因子：
3.7
作者：
Ljungberg K;McBrayer A;Camp JV;Chu YK;Tapp R;Noah DL;Grimes S;Proctor ML;Liljeström P;Jonsson CB;Bruder CE
通讯作者：
Bruder CE
影响因子：
5
作者：
通讯作者：
--
老年人甲型/H1N1 流感特异性 IgG 记忆样 B 细胞反应的转录特征。
影响因子：
5.5
作者：
Haralambieva IH;Ovsyannikova IG;Kennedy RB;Zimmermann MT;Grill DE;Oberg AL;Poland GA
通讯作者：
Poland GA