Synergy of TLR3 and 7 ligands significantly enhances function of DCs to present inactivated PRRSV antigen through TRIF/MyD88-NF-κB signaling pathway

TLR3 和 7 配体的协同作用显著增强了树突状细胞通过 TRIF/MyD88-NF-κB 信号通路呈递灭活 PRRSV 抗原的功能

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作者:Yue Hu, Xiaoyan Cong, Lei Chen, Jing Qi, Xiangju Wu, Mingming Zhou, Dongwan Yoo, Feng Li, Wenbo Sun, Jiaqiang Wu, Xiaomin Zhao, Zhi Chen, Jiang Yu, Yijun Du, Jinbao Wang

Abstract

PRRS is one of the most important diseases in swine industry. Current PRRS inactivated vaccine provides only a limited protection and cannot induce sufficient cell-mediated immune responses. In this study, we first found that the mRNA and protein levels of Th1-type cytokines (IFN-γ, IL-12) and Th2-type cytokines (IL-6, IL-10) were significantly increased through TRIF/MyD88-NF-κB signaling pathway when porcine peripheral blood monocyte-derived dendritic cells (MoDCs) were treated with poly (I: C) of TLR3 ligand and imiquimod of TLR7 ligand, along with inactivated PRRSV antigen. Meanwhile, the ability of catching PRRSV antigen was also significantly enhanced. In mice experiment, it was found that the PRRSV-specific T lymphocyte proliferation, the percentages of CD4(+), CD8(+) T lymphocytes and PRRSV-specific CD3(+) T cells producing IFN-γ and IL-4, the levels of Th1- and Th2-type cytokines and the titers of neutralization antibody were significantly enhanced in poly (I: C), imiquimod along with inactivated PRRSV group. Taken together, results of our experiments described for the first time that synergy of TLR3 and 7 ligands could significantly enhance the function of DCs to present inactivated PRRSV antigen through TRIF/MyD88-NF-κB signaling pathway and be used as adjuvant candidate for the development of novel PRRS inactivated vaccine.

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