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

Nature Immunology volume 7, pages 868874 (2006) | Download Citation



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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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.

Author information

Author notes

    • Satoshi Uematsu
    •  & Myoung Ho Jang

    These authors contributed equally to this work.


  1. Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Suita Osaka 565-0871, Japan.

    • Satoshi Uematsu
    • , Nicolas Chevrier
    • , Yutaro Kumagai
    • , Masahiro Yamamoto
    • , Hiroki Kato
    • , Hiroaki Hemmi
    • , Osamu Takeuchi
    •  & Shizuo Akira
  2. Laboratory of Immunodynamics, Department of Microbiology and Immunology, 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 Osaka 565-0871, Japan.

    • Cevayir Coban
  6. ERATO, Japan Science and Technology Corporation, 3-1 Yamada-oka, Suita Osaka 565-0871, Japan.

    • Taro Kawai
    • , Ken J Ishii
    • , Osamu Takeuchi
    •  & Shizuo Akira


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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.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Shizuo Akira.

Supplementary information

PDF files

  1. 1.

    Supplementary Fig. 1

    Generation of Tlr5−/− mice.

  2. 2.

    Supplementary Fig. 2

    CD11c+ LPCs produce IL-6 in response to TLR2 and TLR9 stimulation.

  3. 3.

    Supplementary Fig. 3

    Surface phenotype of MLN cells 2 d after oral S. typhimurium infection.

  4. 4.

    Supplementary Fig. 4

    Uptake of S. typhimurium in situ.

  5. 5.

    Supplementary Table 1

    Primer sequences.

  6. 6.

    Supplementary Methods

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