Distinct Antigen Delivery Systems Induce Dendritic Cells' Divergent Transcriptional Response: New Insights from a Comparative and Reproducible Computational Analysis.
Distinct Antigen Delivery Systems Induce Dendritic Cells' Divergent Transcriptional Response: New Insights from a Comparative and Reproducible Computational Analysis.
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DOI：
10.3390/ijms18030494
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发表时间：
2017-02-25
影响因子：
5.6
通讯作者：
D'Apice L
中科院分区：
文献类型：
--
作者：
Costa V;Righelli D;Russo F;De Berardinis P;Angelini C;D'Apice L
接种疫苗是预防传染病最成功和最具成本效益的方法。然而，许多疫苗抗原具有较差的体内免疫原性潜力，并且需要佐剂来增强免疫应答。系统生物学在免疫学和疫苗学中的应用已经为疫苗和佐剂的工作机制提供了重要的见解。我们以前的特点是两个安全和强大的传递系统来自非致病性原核生物：E2和FD丝状噬菌体系统。它们引发体内免疫应答，诱导CD 8 + T细胞应答，即使在没有佐剂或树突细胞成熟刺激物的情况下。然而，缺乏对这种激活背后的复杂基因表达网络的系统和比较分析。因此，我们比较了暴露于这些抗原递送系统的离体分离的骨髓来源的树突状细胞的转录组。出现了显着差异，特别是涉及先天免疫，共刺激和细胞因子产生的基因。结果表明，E2驱动极化向Th 2表型，主要介导的Irf 4，Ccl 17，和Ccr 4过表达。相反，fd-scαDEC-205通过诱导IL 12 b、IL 12 rb、IL 6和其他参与其信号转导的分子来触发Th 1 T细胞的极化。使用RNASeqGUI进行数据分析，因此，解决了计算分析的透明度和再现性的日益增长的需求。
Vaccination is the most successful and cost-effective method to prevent infectious diseases. However, many vaccine antigens have poor in vivo immunogenic potential and need adjuvants to enhance immune response. The application of systems biology to immunity and vaccinology has yielded crucial insights about how vaccines and adjuvants work. We have previously characterized two safe and powerful delivery systems derived from non-pathogenic prokaryotic organisms: E2 and fd filamentous bacteriophage systems. They elicit an in vivo immune response inducing CD8+ T-cell responses, even in absence of adjuvants or stimuli for dendritic cells’ maturation. Nonetheless, a systematic and comparative analysis of the complex gene expression network underlying such activation is missing. Therefore, we compared the transcriptomes of ex vivo isolated bone marrow-derived dendritic cells exposed to these antigen delivery systems. Significant differences emerged, especially for genes involved in innate immunity, co-stimulation, and cytokine production. Results indicate that E2 drives polarization toward the Th2 phenotype, mainly mediated by Irf4, Ccl17, and Ccr4 over-expression. Conversely, fd-scαDEC-205 triggers Th1 T cells’ polarization through the induction of Il12b, Il12rb, Il6, and other molecules involved in its signal transduction. The data analysis was performed using RNASeqGUI, hence, addressing the increasing need of transparency and reproducibility of computational analysis.