june 2002 | MARION JURK1*, FLORIAN HEIL2,3#, JORG VOLLMER1, CHRISTIAN SCHETTER1, ARTHUR M. KRIEG1, HERMANN WAGNER2, GRAYSON LIPFORD1 AND STEFAN BAUER2
The study investigates the role of human Toll-like receptors (TLRs) TLR7 and TLR8 in responding to the antiviral compound R-848. TLRs are crucial in the innate immune response to pathogens by detecting pathogen-associated molecular patterns (PAMPs) and activating immune cells through the MyD88-dependent signaling pathway. The research, conducted by Marion Jurk et al., demonstrates that both human TLR7 and TLR8 can independently mediate the recognition of R-848, an imidazoquinoline with antiviral activity. In experiments using HEK293 cells transfected with human TLR8 or TLR7, R-848 induced NF-κB activation in a dose-dependent manner. TLR7 showed higher sensitivity to R-848, while TLR8 was more effective at higher concentrations. However, murine TLR8 did not activate NF-κB in response to R-848, suggesting its non-functionality in mice. These findings indicate a possible redundancy between TLR7 and TLR8, allowing for fine-tuning of the immune response to different concentrations of R-848. Further studies are needed to identify the natural ligands for both receptors and to clarify the function of murine TLR8.The study investigates the role of human Toll-like receptors (TLRs) TLR7 and TLR8 in responding to the antiviral compound R-848. TLRs are crucial in the innate immune response to pathogens by detecting pathogen-associated molecular patterns (PAMPs) and activating immune cells through the MyD88-dependent signaling pathway. The research, conducted by Marion Jurk et al., demonstrates that both human TLR7 and TLR8 can independently mediate the recognition of R-848, an imidazoquinoline with antiviral activity. In experiments using HEK293 cells transfected with human TLR8 or TLR7, R-848 induced NF-κB activation in a dose-dependent manner. TLR7 showed higher sensitivity to R-848, while TLR8 was more effective at higher concentrations. However, murine TLR8 did not activate NF-κB in response to R-848, suggesting its non-functionality in mice. These findings indicate a possible redundancy between TLR7 and TLR8, allowing for fine-tuning of the immune response to different concentrations of R-848. Further studies are needed to identify the natural ligands for both receptors and to clarify the function of murine TLR8.