Small anti-viral compounds activate immune cells via the TLR7 MyD88-dependent signaling pathway.
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.
Hemmi
Hiroaki
H
Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan.
Kaisho
Tsuneyasu
T
Takeuchi
Osamu
O
Sato
Shintaro
S
Sanjo
Hideki
H
Hoshino
Katsuaki
K
Horiuchi
Takao
T
Tomizawa
Hideyuki
H
Takeda
Kiyoshi
K
Akira
Shizuo
S
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
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