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Brief Definitive Report

Interferon- and Interleukin-12 Are Induced Differentially by Toll-like Receptor 7 Ligands in Human Blood Dendritic Cell Subsets

¹ First Department of Internal Medicine, Kansai Medical University, Osaka 570-8506, Japan
² Department of Host Defense, Research Institute for Microbial Diseases, Osaka University
³ Solution-oriented Research for Science and Technology, Japan Science and Technology Corporation, Osaka 565-0871, Japan
⁴ RIKEN Research Center for Allergy and Immunology, Kanagawa 230-0045, Japan
⁵ Pharmaceuticals and Biotechnology Laboratory, Japan Energy Corporation, Saitama 335-8502, Japan

Address correspondence to Ryuichi Amakawa, First Department of Internal Medicine, Kansai Medical University, 10-15 Fumizono-cho, Moriguchi City, Osaka 570-8506, Japan. Phone: 81-6-6993-9453; Fax: 81-6-6994-8344; E-mail: amakawa{at}takii.kmu.ac.jp

Dendritic cells (DCs) play a crucial role in the immune responses against infections by sensing microbial invasion through toll-like receptors (TLRs). In humans, two distinct DC subsets, CD11c^- plasmacytoid DCs (PDCs) and CD11c⁺ myeloid DCs (MDCs), have been identified and can respond to different TLR ligands, depending on the differential expression of cognate TLRs. In this study, we have examined the effect of TLR-7 ligands on human DC subsets. Both subsets expressed TLR-7 and could respond to TLR-7 ligands, which enhanced the survival of the subsets and upregulated the surface expression of costimulatory molecules such as CD40, CD80, and CD86. However, the cytokine induction pattern was distinct in that PDCs and MDCs produced interferon (IFN)- and interleukin (IL)-12, respectively. In response to TLR-7 ligands, the Th1 cell supporting ability of both DC subsets was enhanced, depending on the cytokines the respective subsets produced. This study demonstrates that TLR-7 exerts its biological effect in a DC subset-specific manner.

Key Words: immunity • cytokines • imidazoquinolines • pathogen-associated molecular patterns • Th cell responses

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• Hemmi, H., Kaisho, T., Takeda, K., Akira, S. (2003). The Roles of Toll-Like Receptor 9, MyD88, and DNA-Dependent Protein Kinase Catalytic Subunit in the Effects of Two Distinct CpG DNAs on Dendritic Cell Subsets. J. Immunol. 170: 3059-3064 [Abstract] [Full Text]  
• Mazzoni, A., Leifer, C. A., Mullen, G. E. D., Kennedy, M. N., Klinman, D. M., Segal, D. M. (2003). Cutting Edge: Histamine Inhibits IFN-{alpha} Release from Plasmacytoid Dendritic Cells. J. Immunol. 170: 2269-2273 [Abstract] [Full Text]  
• Tsujimura, H., Tamura, T., Ozato*, K. (2003). Cutting Edge: IFN Consensus Sequence Binding Protein/IFN Regulatory Factor 8 Drives the Development of Type I IFN-Producing Plasmacytoid Dendritic Cells. J. Immunol. 170: 1131-1135 [Abstract] [Full Text]  
• Miller, J. L., Anders, E. M. (2003). Virus-cell interactions in the induction of type 1 interferon by influenza virus in mouse spleen cells. J. Gen. Virol. 84: 193-202 [Abstract] [Full Text]  

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