The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.
Toll‐like receptor 9 binds single‐stranded CpG‐DNA in a sequence‐ and pH‐dependent manner
Open accessAbstract
Toll‐like receptors (TLR) recognize bacterial and viral components, but direct interaction of receptor and ligand is unclear. Here, we demonstrate that TLR9 binds directly and sequence‐specifically to single‐stranded unmethylated CpG‐DNA containing a phosphodiester backbone. TLR9‐CpG‐DNA interaction occurs at the acidic pH (6.5–5.0) found in endosomes and lysosomes. By sequence comparison we identified a potential CpG‐DNA binding domain homologous to that described for methyl‐CpG‐DNA binding proteins. Amino acid substitutions in this region abrogated CpG‐DNA binding and led to loss of NF‐κB activation. Furthermore, chloroquine and quinacrine, therapeutic agents for autoimmune diseases like rheumatoid arthritis and systemic lupus erythematosus, directly blocked TLR9‐CpG‐DNA interaction but not TLR2‐Pam3Cys binding. Our results demonstrate direct binding of TLR9 to CpG‐DNA and suggest that the therapeutic activity of chloroquine and quinacrine in autoimmune diseases may be due to its activity as a TLR9 antagonist and inhibitor of endosomal acidification.
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A Toll-like receptor recognizes bacterial DNA
Hemmi, H., Takeuchi, O., Kawai, T., Kaisho, T., Sato, S., Sanjo, H., Matsumoto, M., Hoshino, K., Wagner, H., Takeda, K., et al. (2000) · Nature · doi:10.1038/35047123 · Cited by 6,491
Self-citationTakeda, K., Kaisho, T., & Akira, S. (2003) · Annual Review of Immunology · doi:10.1146/annurev.immunol.21.120601.141126 · Cited by 6,143
CpG motifs in bacterial DNA trigger direct B-cell activation
Krieg, A. M., Yi, A.-K., Matson, S., Waldschmidt, T. J., Bishop, G. A., Teasdale, R., Koretzky, G. A., & Klinman, D. M. (1995) · Nature · doi:10.1038/374546a0 · Cited by 3,508
Mechanism and Function of a Newly Identified CpG DNA Motif in Human Primary B Cells
Hartmann, G., & Krieg, A. M. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.164.2.944 · Cited by 605
Binding of the Drosophila cytokine Spätzle to Toll is direct and establishes signaling
Weber, A. N. R., Tauszig-Delamasure, S., Hoffmann, J. A., Lelièvre, E., Gascan, H., Ray, K. P., Morse, M. A., Imler, J.-L., & Gay, N. J. (2003) · Nature Immunology · doi:10.1038/ni955 · Cited by 469
Cited by
Assembly and localization of Toll-like receptor signalling complexes
Gay, N. J., Symmons, M. F., Gangloff, M., & Bryant, C. E. (2014) · Nature Reviews Immunology · doi:10.1038/nri3713 · Cited by 832
Mechanism of endosomal TLR inhibition by antimalarial drugs and imidazoquinolines
Kužnik, A., Benčina, M., Švajger, U., Jeras, M., Rozman, B., & Jerala, R. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1000702 · Cited by 606
Bafica, A., Scanga, C. A., Feng, C. G., Leifer, C., Cheever, A., & Sher, A. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20051782 · Cited by 601
Toll-like receptors — taking an evolutionary approach
Leulier, F., & Lemaitre, B. (2008) · Nature Reviews Genetics · doi:10.1038/nrg2303 · Cited by 581
Targeting the innate immune response with improved vaccine adjuvants
Pashine, A., Valiante, N. M., & Ulmer, J. B. (2005) · Nature Medicine · doi:10.1038/nm1210 · Cited by 555
Metadata
- Authors
- Rutz, M., Metzger, J., Gellert, T., Luppa, P., Lipford, G. B., Wagner, H., & Bauer, S.
- Venue
- European Journal of Immunology
- Publisher
- Wiley
- Published
- 2004-08-05
- Volume
- 34
- Issue
- 9
- Pages
- 2541-2550
- ISSN
- 0014-2980 (ISSN-L)
- 1521-4141
- OpenAlex
- W2065423690
- Cited by
- 503
- References
- 5
- FWCI
- 13.12
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Rutz, M., Metzger, J., Gellert, T., Luppa, P., Lipford, G. B., Wagner, H., & Bauer, S. (2004). Toll‐like receptor 9 binds single‐stranded CpG‐DNA in a sequence‐ and pH‐dependent manner. European Journal of Immunology. https://doi.org/10.1002/eji.200425218
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
