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* Laboratory of Host Defense, WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan;
Department of Host Defense,
Department of Molecular Protozoology, and
Exploratory Research for Advanced Technology (ERATO), Japan Science and Technology Agency, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan; and
¶ Respiratory Oncology and Molecular Medicine, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Miyagi, Japan
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-β (TRIF) and IFN-β 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.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 H. K. and S. K. made equal contributions to this work.
2 Address correspondence and reprint requests to Dr. Shizuo Akira, Laboratory of Host Defense, WPI Immunology Frontier Research Center, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan. E-mail address: sakira{at}biken.osaka-u.ac.jp
3 Abbreviations used in this paper: DC, dendritic cell; DKO, double knockout; GM-DC, GM-CSF-induced bone marrow DC; IP-10, IFN-
-inducible protein 10; IPS-1, IFN-β promoter stimulator 1; KO, knockout; Mda5, melanoma differentiation-associated gene 5; poly IC, polyriboinosinic-polyribocytidylic acid; RIG-I; retinoic acid-inducible gene I; TRIF, Toll/IL-1R domain-containing adaptor inducing IFN-β; WT, wild type.
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