Human TLR7 or TLR8 independently confer responsiveness to the antiviral compound R-848 (original) (raw)

Nature Immunology volume 3, page 499 (2002) Cite this article

Toll-like receptors (TLRs) play an important role in the innate immune response to pathogens1. TLRs detect PAMPs (pathogen-associated molecular patterns) and stimulate immune cells via the MyD88-dependent interleukin 1 receptor (IL-1R)–TLR signaling pathway, which leads to activation of the transcription factor NF-κB2. In humans, ten members of this family (TLR1 to TLR10) have been reported to date. TLR2, TLR4 and TLR5 are crucial for the recognition of peptidoglycan, lipopolysaccharide and flagellin, respectively3,4,5. TLR6 associates with TLR2 and recognizes lipoproteins from mycoplasma6. TLR9 detects bacterial DNA containing unmethylated CpG motifs and TLR3 activates immune cells in response to double-stranded RNA7,8,9. The natural ligands for TLR1, TLR7, TLR8 and TLR10 are not known, although a synthetic compound with antiviral activity has now been described as a ligand for TLR710.

Hemmi et al. reported in Nature Immunology that, in experiments that used gene-deficient mice, the antiviral imidazoquinoline resiquimod (R848) activates immune cells via the TLR7 MyD88-dependent signaling pathway10. They showed that macrophages from MyD88- and TLR7-deficient mice do not respond to R848 stimulation, whereas macrophages from wild-type mice strongly induce the transcription factor NF-κB and the secretion of proinflammatory cytokines, such as tumor necrosis factor-α, as well as the regulatory cytokine IL-12. In addition, Hemmi et al. showed, by genetic complementation in HEK293 cells, that human TLR7 confers responsiveness to R84810.

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Figure 1: R-848 induces NF-κB activation via TLR8 or TLR7.

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Author notes

  1. Marion Jurk and Florian Heil: These authors contributed equally to this work.

Authors and Affiliations

  1. Coley Pharmaceutical GmbH, Elisabeth-Selbert-Strasse 9, 40764 Langenfeld, Germany and Coley Pharmaceutical Group, Inc., 93 Worcester St., Wellesley, 02481, MA, USA
    Marion Jurk, Jörg Vollmer, Christian Schetter, Arthur M. Krieg & Grayson Lipford
  2. Institute for Medical Microbiology, Hygiene and Immunology, Trogerstrasse 9, Munich, 81675, Germany
    Florian Heil, Hermann Wagner & Stefan Bauer

Authors

  1. Marion Jurk
  2. Florian Heil
  3. Jörg Vollmer
  4. Christian Schetter
  5. Arthur M. Krieg
  6. Hermann Wagner
  7. Grayson Lipford
  8. Stefan Bauer

Corresponding author

Correspondence toStefan Bauer.

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Jurk, M., Heil, F., Vollmer, J. et al. Human TLR7 or TLR8 independently confer responsiveness to the antiviral compound R-848.Nat Immunol 3, 499 (2002). https://doi.org/10.1038/ni0602-499

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