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International Immunology 2005 17(1):1-14; doi:10.1093/intimm/dxh186
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© 2005 The Japanese Society for Immunology


REVIEW ARTICLE

Toll-like receptors in innate immunity

Kiyoshi Takeda1 and Shizuo Akira2,3

1 Department of Molecular Genetics, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, 2 Department of Host Defense, Research Institute for Microbial Diseases, Osaka University and 3 ERATO, Japan Science and Technology Agency, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan

Corresponding author: S. Akira; E-mail: sakira{at}biken.osaka-u.ac.jp

Functional characterization of Toll-like receptors (TLRs) has established that innate immunity is a skillful system that detects invasion of microbial pathogens. Recognition of microbial components by TLRs initiates signal transduction pathways, which triggers expression of genes. These gene products control innate immune responses and further instruct development of antigen-specific acquired immunity. TLR signaling pathways are finely regulated by TIR domain-containing adaptors, such as MyD88, TIRAP/Mal, TRIF and TRAM. Differential utilization of these TIR domain-containing adaptors provides specificity of individual TLR-mediated signaling pathways. Several mechanisms have been elucidated that negatively control TLR signaling pathways, and thereby prevent overactivation of innate immunity leading to fatal immune disorders. The involvement of TLR-mediated pathways in autoimmune and inflammatory diseases has been proposed. Thus, TLR-mediated activation of innate immunity controls not only host defense against pathogens but also immune disorders.

Keywords: adaptor, innate immunity, signal transduction, TIR domain, Toll-like receptor


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J. Virol.Home page
L. M. Gargano, J. M. Moser, and S. H. Speck
Role for MyD88 Signaling in Murine Gammaherpesvirus 68 Latency
J. Virol., April 15, 2008; 82(8): 3853 - 3863.
[Abstract] [Full Text] [PDF]


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BloodHome page
M. M. Weck, S. Appel, D. Werth, C. Sinzger, A. Bringmann, F. Grunebach, and P. Brossart
hDectin-1 is involved in uptake and cross-presentation of cellular antigens
Blood, April 15, 2008; 111(8): 4264 - 4272.
[Abstract] [Full Text] [PDF]


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BloodHome page
D. Escors, L. Lopes, R. Lin, J. Hiscott, S. Akira, R. J. Davis, and M. K. Collins
Targeting dendritic cell signaling to regulate the response to immunization
Blood, March 15, 2008; 111(6): 3050 - 3061.
[Abstract] [Full Text] [PDF]


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Infect. Immun.Home page
S. S. Yoon and J. J. Mekalanos
Decreased Potency of the Vibrio cholerae Sheathed Flagellum To Trigger Host Innate Immunity
Infect. Immun., March 1, 2008; 76(3): 1282 - 1288.
[Abstract] [Full Text] [PDF]


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Int ImmunolHome page
P. F.-Y. Cheung, C.-K. Wong, W.-K. Ip, and C. W.-K. Lam
FAK-mediated activation of ERK for eosinophil migration: a novel mechanism for infection-induced allergic inflammation
Int. Immunol., March 1, 2008; 20(3): 353 - 363.
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J. Immunol.Home page
N. Semaan, G. Alsaleh, J.-E. Gottenberg, D. Wachsmann, and J. Sibilia
Etk/BMX, a Btk Family Tyrosine Kinase, and Mal Contribute to the Cross-Talk between MyD88 and FAK Pathways
J. Immunol., March 1, 2008; 180(5): 3485 - 3491.
[Abstract] [Full Text] [PDF]


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JEMHome page
S. Hapfelmeier, A. J. Muller, B. Stecher, P. Kaiser, M. Barthel, K. Endt, M. Eberhard, R. Robbiani, C. A. Jacobi, M. Heikenwalder, et al.
Microbe sampling by mucosal dendritic cells is a discrete, MyD88-independent stepin {Delta}invG S. Typhimurium colitis
J. Exp. Med., February 18, 2008; 205(2): 437 - 450.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
S. Thakran, H. Li, C. L. Lavine, M. A. Miller, J. E. Bina, X. R. Bina, and F. Re
Identification of Francisella tularensis Lipoproteins That Stimulate the Toll-like Receptor (TLR) 2/TLR1 Heterodimer
J. Biol. Chem., February 15, 2008; 283(7): 3751 - 3760.
[Abstract] [Full Text] [PDF]


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J. Immunol.Home page
T. Andoh, H. Kishi, K. Motoki, K. Nakanishi, Y. Kuraishi, and A. Muraguchi
Protective Effect of IL-18 on Kainate- and IL-1{beta}-Induced Cerebellar Ataxia in Mice
J. Immunol., February 15, 2008; 180(4): 2322 - 2328.
[Abstract] [Full Text] [PDF]


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CVIHome page
P. Mendez-Samperio, A. Trejo, and A. Perez
Mycobacterium bovis Bacillus Calmette-Guerin Induces CCL5 Secretion via the Toll-Like Receptor 2-NF-{kappa}B and -Jun N-Terminal Kinase Signaling Pathways
Clin. Vaccine Immunol., February 1, 2008; 15(2): 277 - 283.
[Abstract] [Full Text] [PDF]


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Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
B. Petersen, K. D. Bloch, F. Ichinose, H.-S. Shin, M. Shigematsu, A. Bagchi, W. M. Zapol, and J. Hellman
Activation of Toll-like receptor 2 impairs hypoxic pulmonary vasoconstriction in mice
Am J Physiol Lung Cell Mol Physiol, February 1, 2008; 294(2): L300 - L308.
[Abstract] [Full Text] [PDF]


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J. Immunol.Home page
D. Torres, C. Paget, J. Fontaine, T. Mallevaey, T. Matsuoka, T. Maruyama, S. Narumiya, M. Capron, P. Gosset, C. Faveeuw, et al.
Prostaglandin D2 Inhibits the Production of IFN-{gamma} by Invariant NK T Cells: Consequences in the Control of B16 Melanoma
J. Immunol., January 15, 2008; 180(2): 783 - 792.
[Abstract] [Full Text] [PDF]


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Proc. Natl. Acad. Sci. USAHome page
J. N. Leonard, R. Ghirlando, J. Askins, J. K. Bell, D. H. Margulies, D. R. Davies, and D. M. Segal
The TLR3 signaling complex forms by cooperative receptor dimerization
PNAS, January 8, 2008; 105(1): 258 - 263.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
J.-Y. Kim, E. Omori, K. Matsumoto, G. Nunez, and J. Ninomiya-Tsuji
TAK1 Is a Central Mediator of NOD2 Signaling in Epidermal Cells
J. Biol. Chem., January 4, 2008; 283(1): 137 - 144.
[Abstract] [Full Text] [PDF]


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Antimicrob. Agents Chemother.Home page
M. Iyori, H. Kataoka, H. M. Shamsul, K. Kiura, M. Yasuda, T. Nakata, A. Hasebe, and K.-i. Shibata
Resveratrol Modulates Phagocytosis of Bacteria through an NF-{kappa}B-Dependent Gene Program
Antimicrob. Agents Chemother., January 1, 2008; 52(1): 121 - 127.
[Abstract] [Full Text] [PDF]


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CVIHome page
N. Fitzner, S. Clauberg, F. Essmann, J. Liebmann, and V. Kolb-Bachofen
Human Skin Endothelial Cells Can Express All 10 TLR Genes and Respond to Respective Ligands
Clin. Vaccine Immunol., January 1, 2008; 15(1): 138 - 146.
[Abstract] [Full Text] [PDF]


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J. Immunol.Home page
W.-J. Won, M. F. Bachmann, and J. F. Kearney
CD36 Is Differentially Expressed on B Cell Subsets during Development and in Responses to Antigen
J. Immunol., January 1, 2008; 180(1): 230 - 237.
[Abstract] [Full Text] [PDF]


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Int ImmunolHome page
M. Cho, K. Ishida, J. Chen, J. Ohkawa, W. Chen, S. Namiki, A. Kotaki, N. Arai, K.-i. Arai, and Y. Kamogawa-Schifter
SAGE library screening reveals ILT7 as a specific plasmacytoid dendritic cell marker that regulates type I IFN production
Int. Immunol., January 1, 2008; 20(1): 155 - 164.
[Abstract] [Full Text] [PDF]


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Arch Otolaryngol Head Neck SurgHome page
T. Y. Cannon, D. Guttridge, J. Dahlman, J. R. George, V. Lai, C. Shores, P. Buzkova, and M. E. Couch
The Effect of Altered Toll-like Receptor 4 Signaling on Cancer Cachexia
Arch Otolaryngol Head Neck Surg, December 1, 2007; 133(12): 1263 - 1269.
[Abstract] [Full Text] [PDF]


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Int ImmunolHome page
S. Sivori, M. Falco, S. Carlomagno, E. Romeo, L. Moretta, and A. Moretta
Heterogeneity of TLR3 mRNA transcripts and responsiveness to poly (I:C) in human NK cells derived from different donors
Int. Immunol., December 1, 2007; 19(12): 1341 - 1348.
[Abstract] [Full Text] [PDF]


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Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
J. Klesney-Tait and M. Colonna
Uncovering the TREM-1-TLR connection
Am J Physiol Lung Cell Mol Physiol, December 1, 2007; 293(6): L1374 - L1376.
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Am. J. Pathol.Home page
L. Macedo, G. Pinhal-Enfield, V. Alshits, G. Elson, B. N. Cronstein, and S. J. Leibovich
Wound Healing Is Impaired in MyD88-Deficient Mice: A Role for MyD88 in the Regulation of Wound Healing by Adenosine A2A Receptors
Am. J. Pathol., December 1, 2007; 171(6): 1774 - 1788.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
M. T. A. Nguyen, S. Favelyukis, A.-K. Nguyen, D. Reichart, P. A. Scott, A. Jenn, R. Liu-Bryan, C. K. Glass, J. G. Neels, and J. M. Olefsky
A Subpopulation of Macrophages Infiltrates Hypertrophic Adipose Tissue and Is Activated by Free Fatty Acids via Toll-like Receptors 2 and 4 and JNK-dependent Pathways
J. Biol. Chem., November 30, 2007; 282(48): 35279 - 35292.
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Proc. Natl. Acad. Sci. USAHome page
N. Funderburg, M. M. Lederman, Z. Feng, M. G. Drage, J. Jadlowsky, C. V. Harding, A. Weinberg, and S. F. Sieg
Human -defensin-3 activates professional antigen-presenting cells via Toll-like receptors 1 and 2
PNAS, November 20, 2007; 104(47): 18631 - 18635.
[Abstract] [Full Text] [PDF]


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J. Immunol.Home page
J. P. McAleer, D. J. Zammit, L. Lefrancois, R. J. Rossi, and A. T. Vella
The Lipopolysaccharide Adjuvant Effect on T Cells Relies on Nonoverlapping Contributions from the MyD88 Pathway and CD11c+ Cells
J. Immunol., November 15, 2007; 179(10): 6524 - 6535.
[Abstract] [Full Text] [PDF]


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J. Immunol.Home page
K. L. Hokeness-Antonelli, M. J. Crane, A. M. Dragoi, W.-M. Chu, and T. P. Salazar-Mather
IFN-{alpha}beta-Mediated Inflammatory Responses and Antiviral Defense in Liver Is TLR9-Independent but MyD88-Dependent during Murine Cytomegalovirus Infection
J. Immunol., November 1, 2007; 179(9): 6176 - 6183.
[Abstract] [Full Text] [PDF]



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