Adenovirus efficiently transduces plasmacytoid dendritic cells resulting in TLR9-dependent maturation and IFN-α production
Adenovirus efficiently transduces plasmacytoid dendritic cells resulting in TLR9-dependent maturation and IFN-α production
复制标题
DOI：
10.1002/jgm.964
复制
发表时间：
2006-11-01
影响因子：
3.5
通讯作者：
Tueting, Thomas
中科院分区：
文献类型：
--
作者：
Basner-Tschakarjan, Etiena;Gaffal, Evelyn;Tueting, Thomas
重组复制缺陷型腺病毒载体（RecAd）是DNA疫苗接种方法的有吸引力的候选者，因为它们能够激活先天性和适应性免疫系统。在这里，我们探讨recAd的能力，以支持和激活树突状细胞的亚群，即浆细胞样树突状细胞（pDC）和常规的树突状细胞（cDC.Methods）DC来源于骨髓前体细胞在体外的帮助下FLT 3-配体。将分选的pDC和cDC群体以各种感染复数用recAd感染。评估了转导效率、表型成熟和IFN-α以及IL-6的产生。此外，在体内测定DC的活化和细胞毒性T淋巴细胞（CTL）的诱导。Toll样受体（TLR）9在recAd识别中的作用被研究，因为以前已经表明DNA病毒是通过该受体识别的。两种DC亚群均成熟并在与recAd相互作用后产生IFN-α。在不存在TLR 9的情况下，仅在cDC中检测到活化和细胞因子产生，而在pDC中未检测到。重要的是，诱导CD 8 + CTL后，在体内注射recAd是类似的TRL 9缺陷型小鼠相比，野生型controls.Conclusions RecAd可以有效地扩增和激活pDC和CDC。pDC需要TLR 9来检测recAd的存在，而cDC也独立于TLR 9识别recAd。这些独特的免疫刺激特性支持重组Ad作为DNA疫苗方法的载体的未来发展。版权所有（c）2006约翰威利父子有限公司。
Background Recombinant replication-deficient adenoviral vectors (recAd) are attractive candidates for DNA vaccination approaches because they are able to activate the innate and adaptive immune systems. Here we explore the ability of recAd to transduce and activate subsets of dendritic cells, namely plasmacytoid dendritic cells (pDC) and conventional dendritic cells (cDC).Methods DC were derived from bone marrow precursors in vitro with the help of FLT3-ligand. Sorted populations of pDC and cDC were infected with recAd at various multiplicities of infection. Transduction efficiency, phenotypic maturation and production of IFN-alpha as well as IL-6 were assessed. Additionally, activation of DC and induction of cytotoxic T lymphocytes (CTL) were determined in vivo. The role of Toll-like receptor (TLR) 9 in recAd recognition was investigated as it has previously been shown that DNA viruses are recognized via this receptor.Results RecAd can efficiently transduce pDC as well as cDC in vitro. Both DC subsets mature and produce IFN-alpha upon interaction with recAd. In the absence of TLR9, activation and cytokine production was only detected in cDC but not in pDC. Importantly, induction of CD8+ CTL following in vivo injection of recAd was similar in TRL9-deficient mice when compared with wildtype controls.Conclusions RecAd can efficiently transduce and activate both pDC and CDC. pDC required TLR9 to detect the presence of recAd whereas cDC also recognized recAd independently of TLR9. These unique immunostimulatory properties support the future development of recombinant Ad as a vector for DNA vaccine approaches. Copyright (c) 2006 John Wiley & Sons, Ltd.