Polymer-mediated DNA vaccine delivery via bystander cells requires a proper balance between transfection efficiency and cytotoxicity.
Polymer-mediated DNA vaccine delivery via bystander cells requires a proper balance between transfection efficiency and cytotoxicity.
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DOI：
10.1016/j.jconrel.2011.08.037
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发表时间：
2012-01-10
期刊：
影响因子：
--
通讯作者：
Wang C
中科院分区：
文献类型：
--
作者：
Palumbo RN;Zhong X;Wang C
直接靶向树突状细胞是DNA疫苗递送的理想目标，以刺激免疫系统的双臂。然而，树突状细胞通常很难使用非病毒复合物进行转染。在这里，我们表明，用PEI/DNA复合物诱导旁观者细胞如成纤维细胞，导致树突状细胞对模型抗原的有效交叉呈递，随后激活抗原特异性CD 8 + T细胞。与转染的成纤维细胞共培养后，树突状细胞的成熟也受到刺激。这样的结果取决于转染效率和成纤维细胞中复合物诱导的细胞毒性之间的适当平衡。事实上，大量的细胞毒性对于T细胞的交叉呈递和交叉致敏是期望的，甚至是必需的。这项研究说明了一种新的途径，聚合物为基础的DNA疫苗交付通过旁观者细胞没有直接靶向抗原呈递细胞，并强调了利用聚合物诱导的细胞毒性的免疫激活的好处的重要性。
Direct targeting of dendritic cells is an ideal goal for DNA vaccine delivery in order to stimulate both arms of the immune system. However, dendritic cells are often difficult to transfect using nonviral polyplexes. Here we show that transfecting bystander cells such as fibroblasts with PEI/DNA complexes leads to efficient cross-presentation of a model antigen by dendritic cells and subsequent activation of antigen-specific CD8+ T cells. Maturation of dendritic cells is also stimulated after co-culture with transfected fibroblasts. Such outcomes depend on a proper balance between transfection efficiency and polyplex-induced cytotoxicity in the fibroblasts. In fact, substantial cytotoxicity is desirable and even necessary for cross-presentation and cross-priming of T cells. This study illustrates a new pathway of polymer-based DNA vaccine delivery via bystander cells without direct targeting of antigen-presenting cells and highlights the importance of exploiting polymer-induced cytotoxicity for the benefit of immune activation.
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