CpG motif acts as a 'danger signal' and provides a T helper type 1-biased microenvironment for DNA vaccination
CpG motif acts as a 'danger signal' and provides a T helper type 1-biased microenvironment for DNA vaccination
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DOI：
10.1111/j.1365-2567.2005.02150.x
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发表时间：
2005-06-01
期刊：
影响因子：
6.4
通讯作者：
Yuan, ZH
中科院分区：
文献类型：
--
作者：
Liu, L;Zhou, XH;Yuan, ZH
递送DNA疫苗的方法可以影响由疫苗诱导的免疫应答的类型。通过基因枪施用DNA疫苗通常诱导辅助性T细胞2型（Th 2）型反应，而针接种引发Th 1型反应。在目前的研究中，我们发现物理创伤，金粒子轰击和CpG基序可以作为“危险信号”，将炎症细胞招募到受损组织。通过实时逆转录-聚合酶链反应分析来自不同组的引流淋巴结或淋巴结衍生的单核细胞的细胞因子谱显示，虽然基因枪轰击诱导了Th 2型细胞因子微环境，其中引流淋巴结中白细胞介素-4（IL-4）和IL-10 mRNA表达增加，而IL-12和干扰素-γ mRNA表达几乎没有增加，皮内注射以及肌肉皮下注射则相反。我们进一步研究了CpG基序的加入是否可以转换引流淋巴结中基因枪轰击产生的Th 2型细胞因子微环境。结果表明，添加CpG基序可以增加引流淋巴结中IL-12 mRNA的表达，无论是皮内注射，肌肉注射，还是基因枪轰击。这些数据表明，CpG基序的递送诱导引流淋巴结中的Th 1偏向的微环境。总之，CpG基序可以在DNA疫苗接种中充当“危险信号”和Th 1免疫应答增强剂。这些结果有助于解释不同途径的DNA疫苗诱导不同类型免疫应答的机制，为DNA疫苗的应用提供参考。
The method of delivering a DNA vaccine can influence the type of immune response induced by the vaccine. Application of a DNA vaccine by gene gun typically induces a T helper type 2 (Th2)-type reaction, whereas needle inoculation triggers a Th1 response. In the present study, we found that physical trauma, gold-particle bombardment and the CpG motif can act as 'danger signals' that recruit inflammatory cells to damaged tissues. Analysis of the cytokine profiles of draining lymph nodes or lymph-node-derived mononuclear cells from different groups by real-time reverse transcription-polymerase chain reaction revealed that, while gene-gun-bombardment induced a Th2-type cytokine microenvironment with increased interleukin-4 (IL-4) and IL-10 mRNA expression and almost no increase in IL-12 and interferon-gamma mRNA expression in draining lymph nodes, intradermal injection as well as subcutaneous injection of muscle induced the opposite. We further studied whether the addition of the CpG motif can switch the Th2-type cytokine microenvironment produced by gene-gun bombardment in draining lymph nodes. Results showed that the addition of the CpG motif can increase IL-12 mRNA expression in draining lymph nodes whether induced by intradermal injection, intramuscular injection, or gene-gun bombardment. These data suggest that delivery of the CpG motif induced a Th1-biased microenvironment in draining lymph nodes. Taken together, the CpG motif can act as a 'danger signal' and Th1 immune response enhancer in DNA vaccination. These results may help to explain the mechanism of different types of immune response induced by DNA vaccines delivered by different routes and facilitate the application of DNA vaccines.