Contribution of IRF-3 mediated IFNbeta production to DNA vaccine dependent cellular immune responses.
Contribution of IRF-3 mediated IFNbeta production to DNA vaccine dependent cellular immune responses.
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DOI：
10.1016/j.vaccine.2009.01.134
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发表时间：
2009-03-26
期刊：
影响因子：
5.5
通讯作者：
Klinman DM
中科院分区：
文献类型：
--
作者：
Shirota H;Petrenko L;Hattori T;Klinman DM
DNA疫苗激活Ag特异性细胞免疫应答的机制尚不完全清楚。目前的研究结果表明，IRF-3在这一过程中发挥着重要作用。IRF-3依赖性信号传导途径由胞质内DNA的存在触发，并在I型IFN的产生中达到高潮。IRF-3 KO小鼠的DNA疫苗接种引起强烈的Ag特异性体液应答，但CD 4和CD 8 T细胞应答（包括Th 1、Th 2和Th 17细胞因子的产生）严重受损。尽管DNA疫苗编码的免疫原性蛋白的表达在IRF-3 KO与野生型小鼠中相似，但KO动物中的抗原呈递严重受损。该缺陷通过共递送IFNβ编码质粒来补救。这些发现表明，IRF-3/IFNβ途径是DNA疫苗接种后诱导细胞免疫的关键。
The mechanism(s) by which DNA vaccines activate Ag-specific cellular immune responses is incompletely understood. Current findings indicate that IRF-3 plays an important role in this process. The IRF-3 dependent signaling pathway is triggered by the presence of intracytoplasmic DNA, and culminates in the production of type I IFNs. DNA vaccination of IRF-3 KO mice elicits a strong Ag-specific humoral response, yet CD4 and CD8 T cell responses (including the production of Th1, Th2 and Th17 cytokines) are severely impaired. Although expression of the immunogenic protein encoded by the DNA vaccine was similar in IRF-3 KO vs wild type mice, antigen presentation was severely impaired in the KO animals. This defect was remedied by the co-delivery of an IFNβ encoding plasmid. These findings suggest that the IRF-3/IFNβ pathways are key to the induction of cellular immunity following DNA vaccination.
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影响因子：
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作者：
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