© 2005 The Japanese Society for Immunology
REVIEW ARTICLE |
Toll-like receptors in innate immunity
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
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  S. Alper, R. Laws, B. Lackford, W. A. Boyd, P. Dunlap, J. H. Freedman, and D. A. Schwartz Identification of innate immunity genes and pathways using a comparative genomics approach PNAS, May 13, 2008; 105(19): 7016 - 7021. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Peiser, J. Koeck, C. J. Kirschning, B. Wittig, and R. Wanner Human Langerhans cells selectively activated via Toll-like receptor 2 agonists acquire migratory and CD4+T cell stimulatory capacity J. Leukoc. Biol., May 1, 2008; 83(5): 1118 - 1127. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 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. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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. [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
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. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
A. M. Lundberg, S. K. Drexler, C. Monaco, L. M. Williams, S. M. Sacre, M. Feldmann, and B. M. Foxwell Key differences in TLR3/poly I:C signaling and cytokine induction by human primary cells: a phenomenon absent from murine cell systems Blood, November 1, 2007; 110(9): 3245 - 3252. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X.-N. Kong, H.-X. Yan, L. Chen, L.-W. Dong, W. Yang, Q. Liu, L.-X. Yu, D.-D. Huang, S.-Q. Liu, H. Liu, et al. LPS-induced down-regulation of signal regulatory protein {alpha} contributes to innate immune activation in macrophages J. Exp. Med., October 29, 2007; 204(11): 2719 - 2731. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. D. Gilfoy and P. W. Mason West Nile Virus-Induced Interferon Production Is Mediated by the Double-Stranded RNA-Dependent Protein Kinase PKR J. Virol., October 15, 2007; 81(20): 11148 - 11158. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. D. Marshall, D. S. Heeke, M. L. Gesner, B. Livingston, and G. Van Nest Negative regulation of TLR9-mediated IFN-{alpha} induction by a small-molecule, synthetic TLR7 ligand J. Leukoc. Biol., September 1, 2007; 82(3): 497 - 508. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Besson, V. Brault, A. Duchon, D. Togbe, J.-C. Bizot, V. F.J. Quesniaux, B. Ryffel, and Y. Herault Modeling the monosomy for the telomeric part of human chromosome 21 reveals haploinsufficient genes modulating the inflammatory and airway responses Hum. Mol. Genet., September 1, 2007; 16(17): 2040 - 2052. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. Giacaman, A. H. Nobbs, K. F. Ross, and M. C. Herzberg Porphyromonas gingivalis Selectively Up-Regulates the HIV-1 Coreceptor CCR5 in Oral Keratinocytes J. Immunol., August 15, 2007; 179(4): 2542 - 2550. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Meier, G. Alter, N. Frahm, H. Sidhu, B. Li, A. Bagchi, N. Teigen, H. Streeck, H.-J. Stellbrink, J. Hellman, et al. MyD88-Dependent Immune Activation Mediated by Human Immunodeficiency Virus Type 1-Encoded Toll-Like Receptor Ligands J. Virol., August 1, 2007; 81(15): 8180 - 8191. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Chelvarajan, D. Popa, Y. Liu, T. V. Getchell, A. J. Stromberg, and S. Bondada Molecular mechanisms underlying anti-inflammatory phenotype of neonatal splenic macrophages J. Leukoc. Biol., August 1, 2007; 82(2): 403 - 416. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Rodriguez, J. Mages, H. Dietrich, N. Wantia, H. Wagner, R. Lang, and T. Miethke MyD88-dependent changes in the pulmonary transcriptome after infection with Chlamydia pneumoniae Physiol Genomics, July 18, 2007; 30(2): 134 - 145. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Iizuka, C. Nakajima, Y.-M. Iizuka, M. Takase, T. Kato, S. Noda, K. Tanaka, and O. Kanagawa Protection from Lethal Infection by Adoptive Transfer of CD8 T Cells Genetically Engineered to Express Virus-Specific Innate Immune Receptor J. Immunol., July 15, 2007; 179(2): 1122 - 1128. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. von Mutius Asthma and Allergies in Rural Areas of Europe Proceedings of the ATS, July 1, 2007; 4(3): 212 - 216. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. M. Empey, M. Hollifield, and B. A. Garvy Exogenous Heat-Killed Escherichia coli Improves Alveolar Macrophage Activity and Reduces Pneumocystis carinii Lung Burden in Infant Mice Infect. Immun., July 1, 2007; 75(7): 3382 - 3393. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. J. Leppert, J. M. Mansfield, and D. M. Paulnock The Soluble Variant Surface Glycoprotein of African Trypanosomes Is Recognized by a Macrophage Scavenger Receptor and Induces I{kappa}B{alpha} Degradation Independently of TRAF6-Mediated TLR Signaling J. Immunol., July 1, 2007; 179(1): 548 - 556. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Yoneyama and T. Fujita Function of RIG-I-like Receptors in Antiviral Innate Immunity J. Biol. Chem., May 25, 2007; 282(21): 15315 - 15318. [Full Text] [PDF]
|
|
|
|
|
|
D. Kim, M. A. Kim, I.-H. Cho, M. S. Kim, S. Lee, E.-K. Jo, S.-Y. Choi, K. Park, J. S. Kim, S. Akira, et al. A Critical Role of Toll-like Receptor 2 in Nerve Injury-induced Spinal Cord Glial Cell Activation and Pain Hypersensitivity J. Biol. Chem., May 18, 2007; 282(20): 14975 - 14983. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Merx, M. Neumaier, H. Wagner, C. J Kirschning, and P. Ahmad-Nejad Characterization and investigation of single nucleotide polymorphisms and a novel TLR2 mutation in the human TLR2 gene Hum. Mol. Genet., May 15, 2007; 16(10): 1225 - 1232. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Koziczak-Holbro, C. Joyce, A. Gluck, B. Kinzel, M. Muller, C. Tschopp, J. C. Mathison, C. N. Davis, and H. Gram IRAK-4 Kinase Activity Is Required for Interleukin-1 (IL-1) Receptor- and Toll-like Receptor 7-mediated Signaling and Gene Expression J. Biol. Chem., May 4, 2007; 282(18): 13552 - 13560. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. G. Flynn, B. K. McFarlin, and M. M. Markofski State of the Art Reviews: The Anti-Inflammatory Actions of Exercise Training American Journal of Lifestyle Medicine, May 1, 2007; 1(3): 220 - 235. [Abstract] [PDF]
|
|
|
|
|
|
S. Tarang, A. Sodhi, and P. Chauhan Differential expression of Toll-like receptors in murine peritoneal macrophages in vitro on treatment with cisplatin Int. Immunol., May 1, 2007; 19(5): 635 - 643. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Hattermann, S. Picard, M. Borgeat, P. Leclerc, M. Pouliot, and P. Borgeat The Toll-like receptor 7/8-ligand resiquimod (R-848) primes human neutrophils for leukotriene B4, prostaglandin E2 and platelet-activating factor biosynthesis FASEB J, May 1, 2007; 21(7): 1575 - 1585. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K.-i. Arimoto, H. Takahashi, T. Hishiki, H. Konishi, T. Fujita, and K. Shimotohno Negative regulation of the RIG-I signaling by the ubiquitin ligase RNF125 PNAS, May 1, 2007; 104(18): 7500 - 7505. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. M. Weck, F. Grunebach, D. Werth, C. Sinzger, A. Bringmann, and P. Brossart TLR ligands differentially affect uptake and presentation of cellular antigens Blood, May 1, 2007; 109(9): 3890 - 3894. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Zhou, E. A. Kurt-Jones, K. A. Fitzgerald, J. P. Wang, A. M. Cerny, M. Chan, and R. W. Finberg Role of MyD88 in Route-Dependent Susceptibility to Vesicular Stomatitis Virus Infection J. Immunol., April 15, 2007; 178(8): 5173 - 5181. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R.-F. Wang Control of Regulatory T Cells and Cancer Immunity by Toll-Like Receptors Am. Assoc. Cancer Res. Educ. Book, April 14, 2007; 2007(1): 177 - 182. [Full Text] [PDF]
|
|
|
|
 |
|
 J. H. Chang, T. Hampartzoumian, B. Everett, A. Lloyd, P. J. McCluskey, and D. Wakefield Changes in Toll-like Receptor (TLR)-2 and TLR4 Expression and Function but Not Polymorphisms Are Associated with Acute Anterior Uveitis Invest. Ophthalmol. Vis. Sci., April 1, 2007; 48(4): 1711 - 1717. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Valera, A. G. Vigo, S. Alonso, L. Barbolla, M. S. Crespo, and N. Fernandez Peptidoglycan and mannose-based molecular patterns trigger the arachidonic acid cascade in human polymorphonuclear leukocytes J. Leukoc. Biol., April 1, 2007; 81(4): 925 - 933. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Cuesta, Q. M. Nhu, E. Zudaire, S. Polumuri, F. Cuttitta, and S. N. Vogel IFN Regulatory Factor-2 Regulates Macrophage Apoptosis through a STAT1/3- and Caspase-1-Dependent Mechanism J. Immunol., March 15, 2007; 178(6): 3602 - 3611. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. R. Alugupalli, S. Akira, E. Lien, and J. M. Leong MyD88- and Bruton's Tyrosine Kinase-Mediated Signals Are Essential for T Cell-Independent Pathogen-Specific IgM Responses J. Immunol., March 15, 2007; 178(6): 3740 - 3749. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Lemmers, L. Salmena, N. Bidere, H. Su, E. Matysiak-Zablocki, K. Murakami, P. S. Ohashi, A. Jurisicova, M. Lenardo, R. Hakem, et al. Essential Role for Caspase-8 in Toll-like Receptors and NF{kappa}B Signaling J. Biol. Chem., March 9, 2007; 282(10): 7416 - 7423. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. A. Derbigny, S.-C. Hong, M. S. Kerr, M. Temkit, and R. M. Johnson Chlamydia muridarum Infection Elicits a Beta Interferon Response in Murine Oviduct Epithelial Cells Dependent on Interferon Regulatory Factor 3 and TRIF Infect. Immun., March 1, 2007; 75(3): 1280 - 1290. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Hamm, A. Heit, M. Koffler, K. M. Huster, S. Akira, D. H. Busch, H. Wagner, and S. Bauer Immunostimulatory RNA is a potent inducer of antigen-specific cytotoxic and humoral immune response in vivo Int. Immunol., March 1, 2007; 19(3): 297 - 304. [Abstract] [Full Text] [PDF]
|
|