Small anti-viral compounds activate immune cells via the TLR7 MyD88-dependent signaling pathway.
Journal:
Nat. Immunol. 2002 FebAuthors:
Hemmi H, Kaisho T, Takeuchi O, Sato S, Sanjo H, Hoshino K, Horiuchi T, Tomizawa H, Takeda K, Akira S
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 t
...[more]o 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.[less]
Mesh Headings:
Adaptor Proteins, Signal Transducing, Adjuvants, Immunologic, Aminoquinolines, Animals, Antigens, Differentiation, Antiviral Agents, Bone Marrow Cells, Dendritic Cells, Drosophila Proteins, Imidazoles, Interferon Inducers, Macrophages, Peritoneal, Membrane Glycoproteins, Mice, Mice, Mutant Strains, Myeloid Differentiation Factor 88, Receptors, Cell Surface, Receptors, Immunologic, Spleen, Toll-Like Receptor 7, Toll-Like Receptors