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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Gene Expression Omnibus
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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.
The authors declare no competing financial interests.
Generation of Tlr5−/− mice. (PDF 1622 kb)
CD11c+ LPCs produce IL-6 in response to TLR2 and TLR9 stimulation. (PDF 791 kb)
Surface phenotype of MLN cells 2 d after oral S. typhimurium infection. (PDF 1128 kb)
Uptake of S. typhimurium in situ. (PDF 903 kb)
Primer sequences. (PDF 21 kb)
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