Innate immunity against vaccinia virus is mediated by TLR2 and requires TLR-independent production of IFN-β
Innate immunity against vaccinia virus is mediated by TLR2 and requires TLR-independent production of IFN-β
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DOI：
10.1182/blood-2006-06-027136
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发表时间：
2007-01-15
期刊：
影响因子：
20.3
通讯作者：
Yang, Yiping
中科院分区：
文献类型：
--
作者：
Zhu, Jiangao;Martinez, Jennifer;Yang, Yiping
痘苗病毒（VV）已广泛用作传染病和癌症的临床应用中的疫苗载体。先前的研究表明，基于 VV 的疫苗的独特效力在于其有效激活先天免疫系统。然而，VV 如何激活先天免疫途径仍然很大程度上未知。在这项研究中，我们发现 VV 通过 Toll 样受体 (TLR) 依赖性和非依赖性途径引发先天免疫反应。 TLR 途径由 TLR2 和 MyD88 介导，导致促炎性细胞因子的产生，而 TLR 独立途径的激活导致 IFN-β 的分泌。更重要的是，TLR依赖性和非依赖性途径都是激活体内对VV的先天性和适应性免疫所必需的。这些发现首次证明 VV 的先天免疫识别是由 TLR2 介导的，证明一种病原体可以同时靶向 TLR 和非 TLR 先天免疫途径，共同实现宿主防御的有效激活，并为设计有效疫苗提出了潜在的新策略。
Vaccinia virus (VV) has been used extensively as a vaccine vehicle in the clinical application for infectious diseases and cancer. Previous studies have suggested that the unique potency of VV-based vaccine lies in its effective activation of the innate immune system. However, how VV activates innate immune pathways remains largely unknown. In this study, we showed that VV elicited innate immune response through both Toll-like receptor (TLR)-dependent and -independent pathways. The TLR pathway was mediated by TLR2 and MyD88, leading to the production of proinflarnmatory cytokines, whereas activation of the TLR-independent pathway resulted in the secretion of IFN-beta. More importantly, both TLR-dependent and -independent pathways were required for activating innate and adaptive immunity to VV in vivo. These findings represent the first evidence that innate immune recognition of VV is mediated by TLR2, demonstrate that one pathogen can target both TLR and non-TLR innate immune pathways to work together in achieving efficient activation of host defense, and suggest potential new strategies for the design of effective vaccines.