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Science 6 June 2003:
Vol. 300. no. 5625, pp. 1524 - 1525
DOI: 10.1126/science.1085536
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Toll-Like Receptor Signaling Pathways

Gregory M. Barton and Ruslan Medzhitov*

Members of the Toll-like receptor (TLR) family recognize conserved microbial structures, such as bacterial lipopolysaccharide and viral double-stranded RNA, and activate signaling pathways that result in immune responses against microbial infections. All TLRs activate MyD88-dependent pathways to induce a core set of stereotyped responses, such as inflammation. However, individual TLRs can also induce immune responses that are tailored to a given microbial infection. Thus, these receptors are involved in both innate and adaptive immune responses. The mechanisms and components of these varied responses are only partly understood. Given the importance of TLRs in host defense, dissection of the pathways they activate has become an important emerging research focus. TLRs and their pathways are numerous; Science's Signal Transduction Knowledge Environment's TLR Connections Map provides an immediate, clear overview of the known components and relations of this complex system.

Section of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, 300 Cedar Street, CABS660, New Haven, CT 06520, USA.

* To whom correspondence should be addressed. E-mail: ruslan.medzhitov{at}yale.edu

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HIV Impairs TNF-{alpha} Release in Response to Toll-Like Receptor 4 Stimulation in Human Macrophages In Vitro.
S. D. Tachado, J. Zhang, J. Zhu, N. Patel, and H. Koziel (2005)
Am. J. Respir. Cell Mol. Biol. 33, 610-621
   Abstract »    Full Text »    PDF »
Toll-like Receptor 4 Signaling Regulates Cytosolic Phospholipase A2 Activation and Lipid Generation in Lipopolysaccharide-stimulated Macrophages.
H.-Y. Qi and J. H. Shelhamer (2005)
J. Biol. Chem. 280, 38969-38975
   Abstract »    Full Text »    PDF »
Distinct roles for the NF-{kappa}B1 and c-Rel transcription factors in the differentiation and survival of plasmacytoid and conventional dendritic cells activated by TLR-9 signals.
M. O'Keeffe, R. J. Grumont, H. Hochrein, M. Fuchsberger, R. Gugasyan, D. Vremec, K. Shortman, and S. Gerondakis (2005)
Blood 106, 3457-3464
   Abstract »    Full Text »    PDF »
MyD88-Dependent Signaling Contributes to Protection following Bacillus anthracis Spore Challenge of Mice: Implications for Toll-Like Receptor Signaling.
M. A. Hughes, C. S. Green, L. Lowchyj, G. M. Lee, V. K. Grippe, M. F. Smith Jr., L.-Y. Huang, E. T. Harvill, and T. J. Merkel (2005)
Infect. Immun. 73, 7535-7540
   Abstract »    Full Text »    PDF »
Silencing Toll-like Receptor-9 in Pseudomonas aeruginosa Keratitis.
X. Huang, R. P. Barrett, S. A. McClellan, and L. D. Hazlett (2005)
Invest. Ophthalmol. Vis. Sci. 46, 4209-4216
   Abstract »    Full Text »    PDF »
Regulation of the type I IFN induction: a current view.
K. Honda, H. Yanai, A. Takaoka, and T. Taniguchi (2005)
Int. Immunol. 17, 1367-1378
   Abstract »    Full Text »    PDF »
Murine Macrophages Produce Endothelin-1 After Microbial Stimulation.
J. R. Wahl, N. J. Goetsch, H. J. Young, R. J. Van Maanen, J. D. Johnson, A. S. Pea, and A. Brittingham (2005)
Experimental Biology and Medicine 230, 652-658
   Abstract »    Full Text »    PDF »
DLG5 variants do not influence susceptibility to inflammatory bowel disease in the Scottish population.
C L Noble, E R Nimmo, H Drummond, L Smith, I D R Arnott, and J Satsangi (2005)
Gut 54, 1416-1420
   Abstract »    Full Text »    PDF »
Chemokine up-regulation in SARS-coronavirus-infected, monocyte-derived human dendritic cells.
H. K. W. Law, C. Y. Cheung, H. Y. Ng, S. F. Sia, Y. O. Chan, W. Luk, J. M. Nicholls, J. S. M. Peiris, and Y. L. Lau (2005)
Blood 106, 2366-2374
   Abstract »    Full Text »    PDF »
Early onset of inflammation and later involvement of TGF{beta} in Duchenne muscular dystrophy.
Y. -W. Chen, K. Nagaraju, M. Bakay, O. McIntyre, R. Rawat, R. Shi, and E. P. Hoffman (2005)
Neurology 65, 826-834
   Abstract »    Full Text »    PDF »
Achieving Stability of Lipopolysaccharide-Induced NF-{kappa}B Activation.
M. W. Covert, T. H. Leung, J. E. Gaston, and D. Baltimore (2005)
Science 309, 1854-1857
   Abstract »    Full Text »    PDF »
Stimulus Specificity of Gene Expression Programs Determined by Temporal Control of IKK Activity.
S. L. Werner, D. Barken, and A. Hoffmann (2005)
Science 309, 1857-1861
   Abstract »    Full Text »    PDF »
Th1-Like Cytokine Induction by Heat-Killed Brucella abortus Is Dependent on Triggering of TLR9.
L.-Y. Huang, K. J. Ishii, S. Akira, J. Aliberti, and B. Golding (2005)
J. Immunol. 175, 3964-3970
   Abstract »    Full Text »    PDF »
Specific Inhibition of MyD88-Independent Signaling Pathways of TLR3 and TLR4 by Resveratrol: Molecular Targets Are TBK1 and RIP1 in TRIF Complex.
H. S. Youn, J. Y. Lee, K. A. Fitzgerald, H. A. Young, S. Akira, and D. H. Hwang (2005)
J. Immunol. 175, 3339-3346
   Abstract »    Full Text »    PDF »
Direct Stimulation of Human T Cells via TLR5 and TLR7/8: Flagellin and R-848 Up-Regulate Proliferation and IFN-{gamma} Production by Memory CD4+ T Cells.
G. Caron, D. Duluc, I. Fremaux, P. Jeannin, C. David, H. Gascan, and Y. Delneste (2005)
J. Immunol. 175, 1551-1557
   Abstract »    Full Text »    PDF »


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