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.
Pubmed ID: 11812998 RIS Download
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