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Science 300 (5625): 1524-1525

Copyright © 2003 by the American Association for the Advancement of Science

Toll-Like Receptor Signaling Pathways

Gregory M. Barton, and Ruslan Medzhitov*

Abstract: 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}

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J. Biol. Chem. 282, 11618-11628
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Modulation of the Interferon Antiviral Response by the TBK1/IKKi Adaptor Protein TANK.
B. Guo and G. Cheng (2007)
J. Biol. Chem. 282, 11817-11826
   Abstract »    Full Text »    PDF »
Post-induction, Stimulus-specific Regulation of Tumor Necrosis Factor mRNA Expression.
A. V. Tsytsykova, J. V. Falvo, M. Schmidt-Supprian, G. Courtois, D. Thanos, and A. E. Goldfeld (2007)
J. Biol. Chem. 282, 11629-11638
   Abstract »    Full Text »    PDF »
Regulation of innate immunity by MAPK dual-specificity phosphatases: knockout models reveal new tricks of old genes.
K. Salojin and T. Oravecz (2007)
J. Leukoc. Biol. 81, 860-869
   Abstract »    Full Text »    PDF »
S. M. Janciauskiene, I. M. Nita, and T. Stevens (2007)
J. Biol. Chem. 282, 8573-8582
   Abstract »    Full Text »    PDF »
Diet-Induced Increases in Adiposity, but Not Plasma Lipids, Promote Macrophage Infiltration Into White Adipose Tissue.
K. R. Coenen, M. L. Gruen, A. Chait, and A. H. Hasty (2007)
Diabetes 56, 564-573
   Abstract »    Full Text »    PDF »
Histone deacetylase activities are required for innate immune cell control of Th1 but not Th2 effector cell function.
J. L. Brogdon, Y. Xu, S. J. Szabo, S. An, F. Buxton, D. Cohen, and Q. Huang (2007)
Blood 109, 1123-1130
   Abstract »    Full Text »    PDF »
Sequential Modifications in Class II Transactivator Isoform 1 Induced by Lipopolysaccharide Stimulate Major Histocompatibility Complex Class II Transcription in Macrophages.
G. Drozina, J. Kohoutek, T. Nishiya, and B. M. Peterlin (2006)
J. Biol. Chem. 281, 39963-39970
   Abstract »    Full Text »    PDF »
A bacterial carbohydrate links innate and adaptive responses through Toll-like receptor 2.
Q. Wang, R. M. McLoughlin, B. A. Cobb, M. Charrel-Dennis, K. J. Zaleski, D. Golenbock, A. O. Tzianabos, and D. L. Kasper (2006)
J. Exp. Med. 203, 2853-2863
   Abstract »    Full Text »    PDF »
Unique characteristics of Xanthomonas oryzae pv. oryzae AvrXa21 and implications for plant innate immunity.
S.-W. Lee, S.-W. Han, L. E. Bartley, and P. C. Ronald (2006)
PNAS 103, 18395-18400
   Abstract »    Full Text »    PDF »
Mycobacteria directly induce cytoskeletal rearrangements for macrophage spreading and polarization through TLR2-dependent PI3K signaling.
E. B. Lasunskaia, M. N. N. Campos, M. R. M. de Andrade, R. A. DaMatta, T. L. Kipnis, M. Einicker-Lamas, and W. D. Da Silva (2006)
J. Leukoc. Biol. 80, 1480-1490
   Abstract »    Full Text »    PDF »
TLR4 Is Required for Host Resistance in Pseudomonas aeruginosa Keratitis.
X. Huang, W. Du, S. A. McClellan, R. P. Barrett, and L. D. Hazlett (2006)
Invest. Ophthalmol. Vis. Sci. 47, 4910-4916
   Abstract »    Full Text »    PDF »
Renal Collecting Duct Epithelial Cells React to Pyelonephritis-Associated Escherichia coli by Activating Distinct TLR4-Dependent and -Independent Inflammatory Pathways.
C. Chassin, J.-M. Goujon, S. Darche, L. du Merle, M. Bens, F. Cluzeaud, C. Werts, E. Ogier-Denis, C. Le Bouguenec, D. Buzoni-Gatel, et al. (2006)
J. Immunol. 177, 4773-4784
   Abstract »    Full Text »    PDF »
A pathway analysis of poly(I:C)-induced global gene expression change in human peripheral blood mononuclear cells.
C. C. Huang, K. E. Duffy, L. R. San Mateo, B. Y. Amegadzie, R. T. Sarisky, and M. L. Mbow (2006)
Physiol Genomics 26, 125-133
   Abstract »    Full Text »    PDF »
The IRAK-1-BCL10-MALT1-TRAF6-TAK1 Cascade Mediates Signaling to NF-{kappa}B from Toll-like Receptor 4.
W. Dong, Y. Liu, J. Peng, L. Chen, T. Zou, H. Xiao, Z. Liu, W. Li, Y. Bu, and Y. Qi (2006)
J. Biol. Chem. 281, 26029-26040
   Abstract »    Full Text »    PDF »

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