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

被引:341
作者
Uematsu, Satoshi
Jang, Myoung Ho
Chevrier, Nicolas
Guo, Zijin
Kumagai, Yutaro
Yamamoto, Masahiro
Kato, Hiroki
Sougawa, Nagako
Matsui, Hidenori
Kuwata, Hirotaka
Hemmi, Hiroaki
Coban, Cevayir
Kawai, Taro
Ishii, Ken J.
Takeuchi, Osamu
Miyasaka, Masayuki
Takeda, Kiyoshi
Akira, Shizuo [1 ]
机构
[1] Osaka Univ, Microbial Dis Res Inst, Dept Host Def, Suita, Osaka 5650871, Japan
[2] Osaka Univ, Grad Sch Med C8, Dept Microbiol & Immunol, Lab Immunodynam, Suita, Osaka 5650871, Japan
[3] Kitasato Inst, Immunoregulat Lab, Kitasato Inst Life Sci, Minato Ku, Tokyo 1088641, Japan
[4] Kitasato Inst, Grad Sch Infect, Minato Ku, Tokyo 1088641, Japan
[5] Kyushu Univ, Med Inst Bioregulat, Dept Mol Genet, Higashi Ku, Fukuoka 8128582, Japan
[6] Osaka Univ, Combined Program Microbiol & Immunol, 21st Century COE, Suita, Osaka 5650871, Japan
[7] Japan Sci & Technol Corp, ERATO, Suita, Osaka 5650871, Japan
基金
日本学术振兴会;
关键词
D O I
10.1038/ni1362
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Toll-like receptors (TLRs) recognize distinct microbial components and induce innate immune responses. TLR5 is triggered by bacterial flagellin. Here we generated Tlr5(-/-) mice 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.
引用
收藏
页码:868 / 874
页数:7
相关论文
共 28 条
[1]   Pathogen recognition and innate immunity [J].
Akira, S ;
Uematsu, S ;
Takeuchi, O .
CELL, 2006, 124 (04) :783-801
[2]   Evasion of Toll-like receptor 5 by flagellated bacteria [J].
Andersen-Nissen, E ;
Smith, KD ;
Strobe, KL ;
Barrett, SLR ;
Cookson, BT ;
Logan, SM ;
Aderem, A .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (26) :9247-9252
[3]   Immunomodulatory dendritic cells in intestinal lamina propria [J].
Chirdo, FG ;
Millington, OR ;
Beacock-Sharp, H ;
Mowat, AM .
EUROPEAN JOURNAL OF IMMUNOLOGY, 2005, 35 (06) :1831-1840
[4]   Cutting edge: Bacterial flagellin activates basolaterally expressed TLR5 to induce epithelial proinflammatory gene expression [J].
Gewirtz, AT ;
Navas, TA ;
Lyons, S ;
Godowski, PJ ;
Madara, JL .
JOURNAL OF IMMUNOLOGY, 2001, 167 (04) :1882-1885
[5]   Salmonella typhimurium translocates flagellin across intestinal epithelia, inducing a proinflammatory response [J].
Gewirtz, AT ;
Simon, PO ;
Schmitt, CK ;
Taylor, LJ ;
Hagedorn, CH ;
O'Brien, AD ;
Neish, AS ;
Madara, JL .
JOURNAL OF CLINICAL INVESTIGATION, 2001, 107 (01) :99-109
[6]   PLASMID-ASSOCIATED VIRULENCE OF SALMONELLA-TYPHIMURIUM [J].
GULIG, PA ;
CURTISS, R .
INFECTION AND IMMUNITY, 1987, 55 (12) :2891-2901
[7]   A common dominant TLR5 stop codon polymorphism abolishes flagellin signaling and is associated with susceptibility to legionnaires' disease [J].
Hawn, TR ;
Verbon, A ;
Lettinga, KD ;
Zhao, LP ;
Li, SS ;
Laws, RJ ;
Skerrett, SJ ;
Beutler, B ;
Schroeder, L ;
Nachman, A ;
Ozinsky, A ;
Smith, KD ;
Aderem, A .
JOURNAL OF EXPERIMENTAL MEDICINE, 2003, 198 (10) :1563-1572
[8]   The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5 [J].
Hayashi, F ;
Smith, KD ;
Ozinsky, A ;
Hawn, TR ;
Yi, EC ;
Goodlett, DR ;
Eng, JK ;
Akira, S ;
Underhill, DM ;
Aderem, A .
NATURE, 2001, 410 (6832) :1099-1103
[9]   The roles of toll-like receptor 9, MyD88, and DNA-depondent protein kinase catalytic subunit in the effects of two distinct CpG DNAs on dendritic cell subsets [J].
Hemmi, H ;
Kaisho, T ;
Takeda, K ;
Akira, S .
JOURNAL OF IMMUNOLOGY, 2003, 170 (06) :3059-3064
[10]  
Hopkins SA, 2000, CELL MICROBIOL, V2, P59