A Toll-like receptor recognizes bacterial DNA (original) (raw)
- Letter
- Published: 07 December 2000
- Osamu Takeuchi1,2,
- Taro Kawai1,2,
- Tsuneyasu Kaisho1,2,
- Shintaro Sato1,2,
- Hideki Sanjo1,2,
- Makoto Matsumoto1,2,
- Katsuaki Hoshino1,2,
- Hermann Wagner3,
- Kiyoshi Takeda1,2 &
- …
- Shizuo Akira1,2
Nature volume 408, pages 740–745 (2000)Cite this article
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An Erratum to this article was published on 01 February 2001
Abstract
DNA from bacteria has stimulatory effects on mammalian immune cells1,2,3, which depend on the presence of unmethylated CpG dinucleotides in the bacterial DNA. In contrast, mammalian DNA has a low frequency of CpG dinucleotides, and these are mostly methylated; therefore, mammalian DNA does not have immuno-stimulatory activity. CpG DNA induces a strong T-helper-1-like inflammatory response4,5,6,7. Accumulating evidence has revealed the therapeutic potential of CpG DNA as adjuvants for vaccination strategies for cancer, allergy and infectious diseases8,9,10. Despite its promising clinical use, the molecular mechanism by which CpG DNA activates immune cells remains unclear. Here we show that cellular response to CpG DNA is mediated by a Toll-like receptor, TLR9. TLR9-deficient (TLR9-/-) mice did not show any response to CpG DNA, including proliferation of splenocytes, inflammatory cytokine production from macrophages and maturation of dendritic cells. TLR9-/- mice showed resistance to the lethal effect of CpG DNA without any elevation of serum pro-inflammatory cytokine levels. The in vivo CpG-DNA-mediated T-helper type-1 response was also abolished in TLR9-/- mice. Thus, vertebrate immune systems appear to have evolved a specific Toll-like receptor that distinguishes bacterial DNA from self-DNA.
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Acknowledgements
We thank G. B. Lipford for helpful discussions; T. Aoki for secretarial assistance; and N. Tsuji, N. Iwami and E. Nakatani for technical assistance. We also thank Hayashibara Biochemical Laboratories, Inc. for providing anti-IRAK antibody. This work was supported in part by grants from the Ministry of Education, Science, Sports and Culture of Japan, and Research Fellowships of the Japan Society for the Promotion of Science for Young Scientists.
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Authors and Affiliations
- Department of Host Defense, Research Institute for Microbial Diseases, Osaka University,
Hiroaki Hemmi, Osamu Takeuchi, Taro Kawai, Tsuneyasu Kaisho, Shintaro Sato, Hideki Sanjo, Makoto Matsumoto, Katsuaki Hoshino, Kiyoshi Takeda & Shizuo Akira - Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, 3-1 Yamada-oka, Suita, 565-0871, Osaka, Japan
Hiroaki Hemmi, Osamu Takeuchi, Taro Kawai, Tsuneyasu Kaisho, Shintaro Sato, Hideki Sanjo, Makoto Matsumoto, Katsuaki Hoshino, Kiyoshi Takeda & Shizuo Akira - Institute of Medical Microbiology, Immunology and Hygiene, Technical University of Munich, Trogerstr. 9, Munich, D-81675, Germany
Hermann Wagner
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Hemmi, H., Takeuchi, O., Kawai, T. et al. A Toll-like receptor recognizes bacterial DNA.Nature 408, 740–745 (2000). https://doi.org/10.1038/35047123
- Received: 26 June 2000
- Accepted: 03 October 2000
- Issue Date: 07 December 2000
- DOI: https://doi.org/10.1038/35047123