杆状病毒通过TLR9直接激活小鼠NK细胞
Baculovirus directly activates murine NK cells via TLR9
原文发布日期:2017-02-10
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The importance of natural killer (NK) cells in innate immune responses against tumors or viral infections enhances the appeal of NK cell-based immunotherapeutic approaches. We have recently reported that baculovirus (BV)-infected dendritic cells (DCs; BV-DCs) induce antitumor immunity against established tumors in mice. These antitumor effects were CD8+ T-cell and NK cell dependent; however, they were found to be CD4+ T-cell independent. In this study, we investigated the involvement of Toll-like receptor 9 (TLR9) in the process of BV recognition by NK cells. We found that BV directly stimulated NK cells, induced the expression of the activation marker CD69 and promoted interferon-gamma (IFN-γ) production and cytotoxicity. Moreover, TLR9 knockout in mice (tlr9−/− NK cells) inhibited NK cell responses to BV, indicating that TLR9 may have a relevant role in the BV-induced upregulation of NK cell functions. Our data demonstrated for the first time that NK cells directly recognize BV via TLR9, which provides opportunities for the use of this technique as an effective tool for BV-based immunotherapies against malignancies.
自然杀伤细胞(NK细胞)在针对肿瘤或病毒感染的先天性免疫应答中的重要性,增强了基于NK细胞的免疫治疗方法的吸引力。我们近期研究发现,杆状病毒(BV)感染的树突状细胞(BV-DCs)能诱导针对小鼠已成型肿瘤的抗肿瘤免疫。这种抗肿瘤效应依赖CD8+ T细胞和NK细胞,但不依赖CD4+ T细胞。本研究探讨了Toll样受体9(TLR9)在NK细胞识别杆状病毒过程中的作用。我们发现BV能直接激活NK细胞,诱导活化标志物CD69的表达,并促进γ干扰素(IFN-γ)的产生及细胞毒性作用。更重要的是,TLR9基因敲除小鼠(tlr9−/− NK细胞)的NK细胞对BV应答受到抑制,表明TLR9可能在BV诱导的NK细胞功能上调过程中发挥关键作用。我们的数据首次证明NK细胞通过TLR9直接识别BV,这为将该技术作为基于BV的抗恶性肿瘤免疫治疗的有效工具提供了新的可能性。
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