Detection of pathogenic intestinal bacteria by Toll-like receptor 5 on intestinal CD11c+ lamina propria cells (original) (raw)

Nature Immunology volume 7, pages 868–874 (2006)Cite this article

Abstract

Toll-like receptors (TLRs) recognize distinct microbial components and induce innate immune responses. TLR5 is triggered by bacterial flagellin. Here we generated Tlr5 −/− 1mice and assessed TLR5 function in vivo. Unlike other TLRs, TLR5 was not expressed on conventional dendritic cells or macrophages. In contrast, TLR5 was expressed mainly on intestinal CD11c+ lamina propria cells (LPCs). CD11c+ LPCs detected pathogenic bacteria and secreted proinflammatory cytokines in a TLR5-dependent way. However, CD11c+ LPCs do not express TLR4 and did not secrete proinflammatory cytokines after exposure to a commensal bacterium. Notably, transport of pathogenic Salmonella typhimurium from the intestinal tract to mesenteric lymph nodes was impaired in Tlr5 −/− mice. These data suggest that CD11c+ LPCs, via TLR5, detect and are used by pathogenic bacteria in the intestinal lumen.

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Acknowledgements

We thank K. Smith and T. Hawn (Institute for Systems Biology, Seattle, Washington) for providing purified flagellin; C. Sasagawa and T. Suzuki (Institute of Medical Science, Tokyo, Japan) for providing bacteria; members of the DNA-chip Development Center for Infectious Diseases (RIMD, Osaka University, Osaka, Japan) for technical advice; N. Kitagaki for technical assistance; and M. Hashimoto for secretarial assistance. Supported by Special Coordination Funds, the Ministry of Education, Culture, Sports, Science and Technology, and Research Fellowships of the Japan Society for the Promotion of Science for Young Scientists.

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Author notes

  1. Satoshi Uematsu and Myoung Ho Jang: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Suita, 565-0871, Osaka, Japan
    Satoshi Uematsu, Nicolas Chevrier, Yutaro Kumagai, Masahiro Yamamoto, Hiroki Kato, Hiroaki Hemmi, Osamu Takeuchi & Shizuo Akira
  2. Department of Microbiology and Immunology, Laboratory of Immunodynamics, Osaka University Graduate School of Medicine (C8), 2-2, Yamada-oka, Suita, 565-0871, Japan
    Myoung Ho Jang, Zijin Guo, Nagako Sougawa & Masayuki Miyasaka
  3. Laboratory of Immunoregulation, Kitasato Institute for Life Sciences and Graduate School of Infection, Control Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan
    Hidenori Matsui
  4. Department of Molecular Genetics, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
    Hirotaka Kuwata & Kiyoshi Takeda
  5. 21st Century COE, Combined Program on Microbiology and Immunology, Osaka University, 3-1 Yamada-oka, Suita, 565-0871, Osaka, Japan
    Cevayir Coban
  6. ERATO, Japan Science and Technology Corporation, 3-1 Yamada-oka, Suita, 565-0871, Osaka, Japan
    Taro Kawai, Ken J Ishii, Osamu Takeuchi & Shizuo Akira

Authors

  1. Satoshi Uematsu
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  2. Myoung Ho Jang
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  3. Nicolas Chevrier
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  4. Zijin Guo
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  5. Yutaro Kumagai
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  6. Masahiro Yamamoto
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  7. Hiroki Kato
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  8. Nagako Sougawa
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  9. Hidenori Matsui
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  10. Hirotaka Kuwata
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  11. Hiroaki Hemmi
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  12. Cevayir Coban
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  13. Taro Kawai
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  14. Ken J Ishii
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  15. Osamu Takeuchi
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  16. Masayuki Miyasaka
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  17. Kiyoshi Takeda
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  18. Shizuo Akira
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Contributions

S.U. and M.H.J. did most of the experiments to characterize mouse phenotypes; N.C. helped with the quantitative PCR, microarray analysis, isolation of cells and enzyme-linked immunosorbent assays; Z.G. helped to isolate cells and with immunostaining and did the surgical operations for the intestinal loop assay; Y.K. helped with analysis of microarray data; M.Y. helped to generate Tlr5 −/− mice; H.K. helped with the enzyme-linked immunosorbent assays; N.S. helped to isolate cells; H.M. provided S. typhimurium and provided instructions for infection experiments; H.K. helped with the infection experiments; H.H. helped to generate Tlr5 −/− mice; C.C. helped with the infection experiments; T.K., K.J.I. and O.T. provided advice for the experiments; M.M. provided advice for the experiments and manuscript; K.T. helped to generate Tlr5 −/− mice and to design experiments; and S.A. designed all the experiments and prepared the manuscript.

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Correspondence toShizuo Akira.

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Uematsu, S., Jang, M., Chevrier, N. et al. Detection of pathogenic intestinal bacteria by Toll-like receptor 5 on intestinal CD11c+ lamina propria cells.Nat Immunol 7, 868–874 (2006). https://doi.org/10.1038/ni1362

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