Department of Microbiology, University of Washington, Seattle, WA, United States.
Department of Immunology, University of Washington, Seattle, WA, United States.
Front Immunol. 2022 Apr 22;13:861710. doi: 10.3389/fimmu.2022.861710. eCollection 2022.
DNA vaccines elicit antibody, T helper cell responses and CD8 T cell responses. Currently, little is known about the mechanism that DNA vaccines employ to induce adaptive immune responses. Prior studies have demonstrated that () and conventional dendritic cells (cDCs) play critical roles in DNA vaccine induced antibody and T cell responses. activation by double stranded (dsDNA) sensing proteins initiate the production of type I interferon (IFN),but the DC-intrinsic effect of signaling is still unclear. Here, we investigated the role of within cDCs on DNA vaccine induction of antibody and T cell responses. knockout ( ) and conditional knockout mice that lack in cDCs (), were immunized intramuscularly with a DNA vaccine that expressed influenza A nucleoprotein (pNP). Both and mice had significantly lower type I T helper (Th1) type antibody (anti-NP IgG) responses and lower frequencies of Th1 associated T cells (NP-specific IFN-γCD4 T cells) post-immunization than wild type (WT) and mice. In contrast, all mice had similar Th2-type NP-specific (IgG) antibody titers. mice developed significantly lower polyfunctional CD8 T cells than WT, and mice. These findings suggest that within cDCs mediates DNA vaccine induction of type I T helper responses including IFN-γCD4 T cells, and Th1-type IgG antibody responses. The induction of CD8 effector cell responses also require , but not within cDCs. These findings are the first to show that is required within cDCs to mediate DNA vaccine induced Th1 immune responses and provide new insight into the mechanism whereby DNA vaccines induce Th1 responses.
DNA 疫苗可引发抗体、辅助性 T 细胞反应和 CD8 T 细胞反应。目前,人们对 DNA 疫苗诱导适应性免疫反应的机制知之甚少。先前的研究表明,( )和传统树突状细胞 (cDCs) 在 DNA 疫苗诱导的抗体和 T 细胞反应中发挥关键作用。双链 (dsDNA) 感应蛋白对 的激活可引发 I 型干扰素 (IFN)的产生,但 DC 内在的 信号转导作用尚不清楚。在这里,我们研究了 cDCs 内 的作用在 DNA 疫苗诱导抗体和 T 细胞反应中的作用。 敲除 ( )和缺乏 cDCs 中 的条件性敲除小鼠 ( ),通过肌肉内免疫接种表达甲型流感核蛋白 (pNP)的 DNA 疫苗。与野生型 (WT)和 小鼠相比, 和 小鼠的 I 型辅助性 T 细胞 (Th1)型抗体 (抗-NP IgG)反应和 Th1 相关 T 细胞 (NP 特异性 IFN-γCD4 T 细胞)的频率显著降低。相比之下,所有小鼠的 Th2 型 NP 特异性 (IgG)抗体滴度相似。 小鼠产生的多功能 CD8 T 细胞明显低于 WT、 小鼠。这些发现表明,cDCs 内的 介导了包括 IFN-γCD4 T 细胞在内的 I 型辅助性 T 细胞反应,以及 Th1 型 IgG 抗体反应的 DNA 疫苗诱导。CD8 效应细胞反应的诱导也需要 ,但不需要 cDCs 内的 。这些发现首次表明 是 cDCs 内介导 DNA 疫苗诱导 Th1 免疫反应所必需的,并为 DNA 疫苗诱导 Th1 反应的机制提供了新的见解。