The imidazoquinoline compounds imiquimod and R-848 are low-molecular-weight immune response modifiers that can induce the synthesis of interferon-α and other cytokines in a variety of cell types. These compounds have potent anti-viral and anti-tumor properties; however, the mechanisms by which they exert their anti-viral activities remain unclear. Here we show that the imidazoquinolines activate immune cells via the Toll-like receptor 7 (TLR7)-MyD88–dependent signaling pathway. In response to the imidazoquinolines, neither MyD88- nor TLR7-deficient mice showed any inflammatory cytokine production by macrophages, proliferation of splenocytes or maturation of dendritic cells. Imidazoquinoline-induced signaling events were also abolished in both MyD88- and TLR7-deficient mice.
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We thank Sumitomo Pharmaceuticals for valuable discussions of this work; E. Horita for secretarial assistance; N. Tsuji and N. Iwami for technical assistance; and Hayashibara Biochemical Laboratories for the antibody to IRAK. Supported in part by grants from Special Coordination Founds for Promoting Science and Technology; the Ministry of Education, Culture, Sports, Science and Technology of Japan; and the Japan Society for the Promotion of Science for Young Scientists.
The authors declare no competing financial interests.
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Hemmi, H., Kaisho, T., Takeuchi, O. et al. Small anti-viral compounds activate immune cells via the TLR7 MyD88–dependent signaling pathway. Nat Immunol 3, 196–200 (2002). https://doi.org/10.1038/ni758
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