Kumar Himanshu, Koyama Shohei, Ishii Ken J, Kawai Taro, Akira Shizuo
Laboratory of Host Defense, WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan.
J Immunol. 2008 Jan 15;180(2):683-7. doi: 10.4049/jimmunol.180.2.683.
Double-stranded RNA, polyriboinosinic-polyribocytidylic acid (poly IC), acts as an adjuvant that enhances adaptive immune responses. The recognition of poly IC is mediated by endosomal TLR3 and cytoplasmic RNA helicase melanoma differentiation-associated gene 5 (Mda5), which signal through the adaptors Toll/IL-1R domain-containing adaptor inducing IFN-beta (TRIF) and IFN-beta promoter stimulator-1 (IPS-1), respectively. However, the contribution of these pathways to the adjuvant effects of poly IC remains unclear. In this study, we found that poly IC-enhanced, Ag-specific Ab production was severely decreased in IPS-1-deficient mice but not in TRIF-deficient mice. However, the double deficiency resulted in a complete loss of Ab production. Furthermore, Ag-specific CD8+ T cell expansion was reduced in both IPS-1-deficient and TRIF-deficient mice and entirely abrogated in the doubly deficient mice. Taken together, these results demonstrate that the adjuvant effects of poly IC require a cooperative activation of TLR and cytoplasmic RNA helicase pathways.
双链RNA，聚肌苷酸-聚胞苷酸（poly IC），作为一种增强适应性免疫反应的佐剂。poly IC的识别由内体Toll样受体3（TLR3）和细胞质RNA解旋酶黑色素瘤分化相关基因5（Mda5）介导，它们分别通过接头含Toll/IL-1受体结构域的接头分子诱导IFN-β（TRIF）和IFN-β启动子刺激因子-1（IPS-1）发出信号。然而，这些途径对poly IC佐剂效应的贡献仍不清楚。在本研究中，我们发现poly IC增强的抗原特异性抗体产生在IPS-1缺陷小鼠中严重降低，但在TRIF缺陷小鼠中没有。然而，双缺陷导致抗体产生完全丧失。此外，抗原特异性CD8 + T细胞扩增在IPS-1缺陷和TRIF缺陷小鼠中均减少，在双缺陷小鼠中完全消除。综上所述，这些结果表明poly IC的佐剂效应需要TLR和细胞质RNA解旋酶途径的协同激活。
