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新城疫病毒样颗粒通过TLR4/NF-κB途径诱导树突状细胞成熟,并通过CCR7-CCL19/CCL21轴促进树突状细胞迁移。

Newcastle disease virus-like particles induce DC maturation through TLR4/NF-κB pathway and facilitate DC migration by CCR7-CCL19/CCL21 axis.

作者信息

Qian Jing, Xu Xiaohong, Ding Jiaxin, Yin Renfu, Sun Yixue, Xue Cong, Wang Jianzhong, Ding Chan, Yu Shengqing, Liu Xiufan, Hu Shunlin, Wang Chunfeng, Cong Yanlong, Ding Zhuang

机构信息

Laboratory of Infectious Diseases, College of Veterinary Medicine, Key Laboratory of Zoonosis Research, Ministry of Education, Jilin University, Changchun 130062, China.

Engineering Research Center of Jilin Province for Animals Probiotics, College of Animal Science and Technology, Jilin Agricultural University, Changchun 130118, China.

出版信息

Vet Microbiol. 2017 May;203:158-166. doi: 10.1016/j.vetmic.2017.03.002. Epub 2017 Mar 4.

DOI:10.1016/j.vetmic.2017.03.002
PMID:28619138
Abstract

Newcastle disease virus-like particles (NDV VLPs) are a potential candidate vaccine, as shown by eliciting specific immune response against NDV in mice and chickens. Activation of dendritic cells (DCs) is critical to initiate immune response. However, the mechanism of how NDV VLPs induce DC maturation and migration remains elusive. In this study, we found that NDV VLPs are efficient in DC activation by up-regulating surface MHC II and costimulatory molecules, and proinflammatory cytokines through the TLR4/NF-κB pathway. Furthermore, NDV VLPs elevated CCR7 expression on DCs, resulting in DC migration towards CCL19/CCL21 both in vitro and ex vivo. As a consequence of DC maturation and migration, CD4+ T cells were also activated in vivo, demonstrating increased intracellular IFN-γ and IL-4 levels. Together, these results present new insights for NDV VLPs induced DC maturation and migration, providing a better understanding of VLP-triggered innate immune responses.

摘要

新城疫病毒样颗粒(NDV VLPs)是一种潜在的候选疫苗,在小鼠和鸡中可引发针对新城疫病毒的特异性免疫反应。树突状细胞(DCs)的激活对于启动免疫反应至关重要。然而,NDV VLPs如何诱导DC成熟和迁移的机制仍不清楚。在本研究中,我们发现NDV VLPs通过TLR4/NF-κB途径上调表面MHC II和共刺激分子以及促炎细胞因子,从而有效地激活DC。此外,NDV VLPs提高了DC上CCR7的表达,导致DC在体外和体内均向CCL19/CCL21迁移。由于DC的成熟和迁移,CD4+ T细胞在体内也被激活,表现为细胞内IFN-γ和IL-4水平升高。总之,这些结果为NDV VLPs诱导DC成熟和迁移提供了新的见解,有助于更好地理解VLP触发的先天性免疫反应。

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