title: Small anti-viral compounds activate immune cells via the TLR7 MyD88-dependent signaling pathway.
abstract: The imidazoquinoline compounds imiquimod and R-848 are low-molecular-weight immune response modifiers that can induce the synthesis of interferon-alpha 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.
authors.affiliation: Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Hemmi
authors.forename: Tsuneyasu
authors.initials: T
authors.lastname: Kaisho
authors.forename: Osamu
authors.initials: O
authors.lastname: Takeuchi
authors.forename: Shintaro
authors.initials: S
authors.lastname: Sato
authors.forename: Hideki
authors.initials: H
authors.lastname: Sanjo
authors.forename: Katsuaki
authors.initials: K
authors.lastname: Hoshino
authors.forename: Takao
authors.initials: T
authors.lastname: Horiuchi
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Tomizawa
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Takeda
authors.forename: Shizuo
authors.initials: S
authors.lastname: Akira
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000276:Adjuvants, Immunologic; D000634:Aminoquinolines / Q000276:immunology*; D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism*; D000998:Antiviral Agents / Q000276:immunology*; D001854:Bone Marrow Cells / Q000276:immunology; D003713:Dendritic Cells; D029721:Drosophila Proteins; D007093:Imidazoles / Q000276:immunology*; D000077271:Imiquimod; D007369:Interferon Inducers / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000276:immunology; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D053594:Myeloid Differentiation Factor 88; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000378:metabolism*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D051199:Toll-Like Receptor 7; D051193:Toll-Like Receptors
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000276:Adjuvants, Immunologic; D000634:Aminoquinolines; D000943:Antigens, Differentiation; D000998:Antiviral Agents; D029721:Drosophila Proteins; D007093:Imidazoles; D007369:Interferon Inducers; D008562:Membrane Glycoproteins; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D051199:Toll-Like Receptor 7; D051193:Toll-Like Receptors; D000077271:Imiquimod; C402365:resiquimod