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Science 5 March 2004:
Vol. 303. no. 5663, pp. 1522 - 1526
DOI: 10.1126/science.1094351
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Reports

A Toll-like Receptor That Prevents Infection by Uropathogenic Bacteria

Dekai Zhang, Guolong Zhang,* Matthew S. Hayden, Matthew B. Greenblatt, Crystal Bussey, Richard A. Flavell, Sankar Ghosh{dagger}

Toll-like receptors (TLRs) recognize molecular patterns displayed by microorganisms, and their subsequent activation leads to the transcription of appropriate host-defense genes. Here we report the cloning and characterization of a member of the mammalian TLR family, TLR11, that displays a distinct pattern of expression in macrophages and liver, kidney, and bladder epithelial cells. Cells expressing TLR11 fail to respond to known TLR ligands but instead respond specifically to uropathogenic bacteria. Mice lacking TLR11 are highly susceptible to infection of the kidneys by uropathogenic bacteria, indicating a potentially important role for TLR11 in preventing infection of internal organs of the urogenital system.

Section of Immunobiology and Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06520, USA.



* Present address: Department of Animal Science, Oklahoma State University, Stillwater, OK 74078, USA.

{dagger} To whom correspondence should be addressed: sankar.ghosh{at}yale.edu.

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H.-J. Anders and P. S. Patole (2005)
Nephrol. Dial. Transplant. 20, 1529-1532
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BACTERIAL INTERACTIONS WITH CELLS OF THE INTESTINAL MUCOSA: TOLL-LIKE RECEPTORS AND NOD2.
E Cario (2005)
Gut 54, 1182-1193
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The evolution of vertebrate Toll-like receptors.
J. C. Roach, G. Glusman, L. Rowen, A. Kaur, M. K. Purcell, K. D. Smith, L. E. Hood, and A. Aderem (2005)
PNAS 102, 9577-9582
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Recognition of Staphylococcus aureus by the Innate Immune System.
B. Fournier and D. J. Philpott (2005)
Clin. Microbiol. Rev. 18, 521-540
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Suppression of Bladder Epithelial Cytokine Responses by Uropathogenic Escherichia coli.
D. A. Hunstad, S. S. Justice, C. S. Hung, S. R. Lauer, and S. J. Hultgren (2005)
Infect. Immun. 73, 3999-4006
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SIGIRR Inhibits Interleukin-1 Receptor- and Toll-like Receptor 4-mediated Signaling through Different Mechanisms.
J. Qin, Y. Qian, J. Yao, C. Grace, and X. Li (2005)
J. Biol. Chem. 280, 25233-25241
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TLR11 Activation of Dendritic Cells by a Protozoan Profilin-Like Protein.
F. Yarovinsky, D. Zhang, J. F. Andersen, G. L. Bannenberg, C. N. Serhan, M. S. Hayden, S. Hieny, F. S. Sutterwala, R. A. Flavell, S. Ghosh, et al. (2005)
Science 308, 1626-1629
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Identification and Functional Characterization of Chicken Toll-Like Receptor 5 Reveals a Fundamental Role in the Biology of Infection with Salmonella enterica Serovar Typhimurium.
M. Iqbal, V. J. Philbin, G. S. K. Withanage, P. Wigley, R. K. Beal, M. J. Goodchild, P. Barrow, I. McConnell, D. J. Maskell, J. Young, et al. (2005)
Infect. Immun. 73, 2344-2350
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Enterococcus faecalis Tropism for the Kidneys in the Urinary Tract of C57BL/6J Mice.
A. L. Kau, S. M. Martin, W. Lyon, E. Hayes, M. G. Caparon, and S. J. Hultgren (2005)
Infect. Immun. 73, 2461-2468
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The role of epithelial Toll-like receptor expression in host defense and microbial tolerance.
M. W. Hornef and C. Bogdan (2005)
Innate Immunity 11, 124-128
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Plasmacytoid Dendritic Cells Control TLR7 Sensitivity of Naive B Cells via Type I IFN.
I. B. Bekeredjian-Ding, M. Wagner, V. Hornung, T. Giese, M. Schnurr, S. Endres, and G. Hartmann (2005)
J. Immunol. 174, 4043-4050
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Vaccinia virus protein A46R targets multiple Toll-like-interleukin-1 receptor adaptors and contributes to virulence.
J. Stack, I. R. Haga, M. Schroder, N. W. Bartlett, G. Maloney, P. C. Reading, K. A. Fitzgerald, G. L. Smith, and A. G. Bowie (2005)
J. Exp. Med. 201, 1007-1018
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Involvement of the Toll-Like Receptor 9 Signaling Pathway in the Induction of Innate Immunity by Baculovirus.
T. Abe, H. Hemmi, H. Miyamoto, K. Moriishi, S. Tamura, H. Takaku, S. Akira, and Y. Matsuura (2005)
J. Virol. 79, 2847-2858
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MyD88 Expression Is Required for Efficient Cross-Presentation of Viral Antigens from Infected Cells.
M. Chen, C. Barnfield, T. I. Naslund, M. N. Fleeton, and P. Liljestrom (2005)
J. Virol. 79, 2964-2972
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Thematic review series: The Immune System and Atherogenesis. Paying the price for pathogen protection: toll receptors in atherogenesis.
P. Tobias and L. K. Curtiss (2005)
J. Lipid Res. 46, 404-411
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Activation of Toll-Like Receptor (TLR)2, TLR4, and TLR9 in the Mammalian Cornea Induces MyD88-Dependent Corneal Inflammation.
A. C. Johnson, F. P. Heinzel, E. Diaconu, Y. Sun, A. G. Hise, D. Golenbock, J. H. Lass, and E. Pearlman (2005)
Invest. Ophthalmol. Vis. Sci. 46, 589-595
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