Mammalian Toll-like receptors

Current Opinion in Immunology

Volumn 15, Issue 1, 2003, Pages 5-11

  Akira, Shizuo ^a  

^a JAPAN SCIENCE AND TECHNOLOGY AGENCY   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

ANTINEOPLASTIC AGENT; ANTIVIRUS AGENT; BROPIRIMINE; GLYCOPROTEIN GP 96; HEAT SHOCK PROTEIN; HEAT SHOCK PROTEIN 60; HEAT SHOCK PROTEIN 70; HEAT SHOCK PROTEIN 90; IMIQUIMOD; LOXORIBINE; RESIQUIMOD; TOLL LIKE RECEPTOR; TOLL LIKE RECEPTOR 1; TOLL LIKE RECEPTOR 2; TOLL LIKE RECEPTOR 3; TOLL LIKE RECEPTOR 4; TOLL LIKE RECEPTOR 5; TOLL LIKE RECEPTOR 6; TOLL LIKE RECEPTOR 7; TOLL LIKE RECEPTOR 9; UNCLASSIFIED DRUG; CELL SURFACE RECEPTOR; MEMBRANE ANTIGEN; MEMBRANE PROTEIN;

ANTINEOPLASTIC ACTIVITY; ANTIVIRAL ACTIVITY; BACTERIUM; CONDYLOMA; DRUG STRUCTURE; FUNGUS; GENE EXPRESSION; HOST RESISTANCE; HUMAN; IMMUNE SYSTEM; INFLAMMATION; MICROORGANISM; MOLECULAR DYNAMICS; NONHUMAN; PROTEIN FAMILY; PROTEIN FUNCTION; PROTEIN LOCALIZATION; REVIEW; VIRUS; VIRUS INFECTION; ANIMAL; BACTERIAL INFECTION; CELL COMMUNICATION; GENE EXPRESSION REGULATION; GENETICS; IMMUNOLOGY; INNATE IMMUNITY; SIGNAL TRANSDUCTION;

ANIMALS; ANTIGENS, SURFACE; BACTERIAL INFECTIONS; CELL COMMUNICATION; GENE EXPRESSION REGULATION; IMMUNITY, NATURAL; MEMBRANE GLYCOPROTEINS; RECEPTORS, CELL SURFACE; SIGNAL TRANSDUCTION; TOLL-LIKE RECEPTORS;

EID: 0037290876     PISSN: 09527915     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0952-7915(02)00013-4     Document Type: Review

References (54)

1. Janeway C.A. Jr., Medzhitov R. Innate immune recognition. Annu. Rev. Immunol. 20:2000;197-216.
2. Aderem A., Ulevitch R.J. Toll-like receptors in the induction of the innate immune response. Nature. 406:2000;782-787.
3. Akira S., Takeda K., Kaisho T. Toll-like receptors: critical proteins linking innate and acquired immunity. Nat. Immunol. 2:2001;675-680.
4. Poltorak A., He X., Smirnova I., Liu M.Y., Huffel C.V., Du X., Birdwell D., Alejos E., Silva M., Galanos C.et al. Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science. 282:1998;2085-2088.
5. Hoshino K., Takeuchi O., Kawai T., Sanjo H., Ogawa T., Takeda Y., Takeda K., Akira S. Cutting edge: Toll-like receptor 4 (TLR4)-deficient mice are hyporesponsive to lipopolysaccharide: evidence for TLR4 as the LPS gene product. J. Immunol. 162:1999;3749-3752.
6. Shimazu R., Akashi S., Ogata H., Nagai Y., Fukudome K., Miyake K., Kimoto M. MD-2, a molecule that confers lipopolysaccharide responsiveness on Toll-like receptor 4. J. Exp. Med. 189:1999;1777-1782.
7. Nagai Y., Akashi S., Nagafuku M., Ogata M., Iwakura Y., Akira S., Kitamura T., Kosugi A., Kimoto M., Miyake K. Essential role of MD-2 in LPS responsiveness and TLR4 distribution. Nat. Immunol. 3:2002;667-672 This paper shows that MD-2 is essential for both the TLR4 response to LPS (but not to other bacterial components such as peptidoglycan and CpG DNA) and the trafficking of TLR4 to the cell surface.
8. Poltorak A., Ricciardi-Castagnoli P., Citterio S., Beutler B. Physical contact between lipopolysaccharide and Toll-like receptor 4 revealed by genetic complementation. Proc. Natl. Acad. Sci. U.S.A. 97:2000;2163-2167.
9. Kawasaki K., Akashi S., Shimazu R., Yoshida T., Miyake K., Nishijima M. Mouse Toll-like receptor 4-MD-2 complex mediates lipopolysaccharide-mimetic signal transduction by Taxol. J. Biol. Chem. 275:2000;2251-2254.
10. Hajjar A.M., Ernst R.K., Tsai J.H., Wilson C.B., Miller S.I. Human Toll-like receptor 4 recognizes host-specific LPS modifications. Nat. Immunol. 3:2002;354-359.
11. Triantafilou M., Triantafilou K. Lipopolysaccharide recognition: CD14, TLRs and the LPS-activation cluster. Trends Immunol. 23:2002;301-304.
12. Ozinsky A., Underhill D.M., Fontenot J.D., Hajjar A.M., Smith K.D., Wilson C.B., Schroeder L., Aderem A. The repertoire for pattern recognition of pathogens by the innate immune system is defined by cooperation between Toll-like receptors. Proc. Natl. Acad. Sci. U.S.A. 97:2000;13766-13771.
13. Takeuchi O., Kawai T., Muhlradt P.F., Morr M., Radolf J.D., Zychlinsky A., Takeda K., Akira S. Discrimination of bacterial lipoproteins by Toll-like receptor 6. Int. Immunol. 13:2001;933-940.
14. •].
15. •] show that, in co-operation with TLR2, TLR1 is involved in the recognition of tri-acylated lipoproteins.
16. Hayashi F., Smith K.D., Ozinsky A., Hawn T.R., Yi E.C., Goodlett D.R., Eng J.K., Akira S., Underhill D.M., Aderem A. The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5. Nature. 410:2001;1099-1103.
17. Gewirtz A.T., Navas T.A., Lyons S., Godowski P.J., Madara J.L. Cutting edge: bacterial flagellin activates basolaterally expressed TLR5 to induce epithelial proinflammatory gene expression. J. Immunol. 167:2001;1882-1885.
18. Hemmi H., Takeuchi O., Kawai T., Kaisho T., Sato S., Sanjo H., Matsumoto M., Hoshino K., Wagner H., Takeda K.et al. A Toll-like receptor recognizes bacterial DNA. Nature. 408:2000;740-745.
19. Bauer S., Kirschning C.J., Hacker H., Redecke V., Hausmann S., Akira S., Wagner H., Lipford G.B. Human TLR9 confers responsiveness to bacterial DNA via species-specific CpG motif recognition. Proc. Natl. Acad. Sci. U.S.A. 98:2001;9237-9242.
20. Alexopoulou L., Holt A.C., Medzhitov R., Flavell R.A. Recognition of double-stranded RNA and activation of NF-κB by Toll-like receptor 3. Nature. 413:2001;732-738 The authors demonstrate that TLR3 is involved in the response to double-stranded RNA, thereby implying that TLR3 has a role in the recognition of viral invasion.
21. Hemmi H., Kaisho T., Takeuchi O., Sato S., Sanjo H., Hoshino K., Horiuchi T., Tomizawa H., Takeda K., Akira S. Small anti-viral compounds activate immune cells via the TLR7 MyD88-dependent signaling pathway. Nat. Immunol. 3:2002;196-200 In this paper, TLR7 is shown to be essential for responses to antiviral chemical compounds that are already in clinical use for the treatment of genital warts caused by human papilloma viruses. This reinforces the idea that TLRs participate in the detection of viral infection, although the natural ligand of TLR7 remains unknown.
22. Wallin R.P., Lundqvist A., More S.H., von Bonin A., Kiessling R., Ljunggren H.G. Heat-shock proteins as activators of the innate immune system. Trends Immunol. 23:2002;130-135.
23. Johnson G.B., Brunn G.J., Kodaira Y., Platt J.L. Receptor-mediated monitoring of tissue well-being via detection of soluble heparan sulfate by Toll-like receptor 4. J. Immunol. 168:2002;5233-5239.
24. Okamura Y., Watari M., Jerud E.S., Young D.W., Ishizaka S.T., Rose J., Chow J.C., Strauss J.F. III The extra domain A of fibronectin activates Toll-like receptor 4. J. Biol. Chem. 276:2001;10229-10233.
25. Termeer C., Benedix F., Sleeman J., Fieber C., Voith U., Ahrens T., Miyake K., Freudenberg M., Galanos C., Simon J.C. Oligosaccharides of Hyaluronan activate dendritic cells via Toll-like receptor 4. J. Exp. Med. 195:2002;99-111.
26. Smiley S.T., King J.A., Hancock W.W. Fibrinogen stimulates macrophage chemokine secretion through Toll-like receptor 4. J. Immunol. 167:2001;2887-2894.
27. Matzinger P. Tolerance, danger, and the extended family. Annu. Rev. Immunol. 12:1994;991-1045.
28. Ahmad-Nejad P., Hacker H., Rutz M., Bauer S., Vabulas R.M., Wagner H. Bacterial CpG-DNA and lipopolysaccharides activate Toll-like receptors at distinct cellular compartments. Eur. J. Immunol. 32:2002;1958-1968.
29. Hacker H., Mischak H., Miethke T., Liptay S., Schmid R., Sparwasser T., Heeg K., Lipford G.B., Wagner H. CpG-DNA-specific activation of antigen-presenting cells requires stress kinase activity and is preceded by non-specific endocytosis and endosomal maturation. EMBO J. 17:1998;6230-6240.
30. Randow F., Seed B. Endoplasmic reticulum chaperone gp96 is required for innate immunity but not cell viability. Nat. Cell Biol. 3:2001;891-896.
31. Hornef M.W., Frisan T., Vandewalle A., Normark S., Richter-Dahlfors A. Toll-like receptor 4 resides in the Golgi apparatus and colocalizes with internalized lipopolysaccharide in intestinal epithelial cells. J. Exp. Med. 195:2002;559-570.
32. Cowan D.B., Noria S., Stamm C., Garcia L.M., Poutias D.N., del Nido P.J., McGowan F.X. Jr. Lipopolysaccharide internalization activates endotoxin-dependent signal transduction in cardiomyocytes. Circ. Res. 88:2001;491-498.
33. Inohara N., Ogura Y., Nunez G. Nods: a family of cytosolic proteins that regulate the host response to pathogens. Curr. Opin. Microbiol. 5:2002;76-80.
34. Hugot J.P., Chamaillard M., Zouali H., Lesage S., Cezard J.P., Belaiche J., Almer S., Tysk C., O'Morain C.A., Gassull M.et al. Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease. Nature. 411:2001;599-603.
35. Re F., Strominger J.L. Toll-like receptor 2 (TLR2) and TLR4 differentially activate human dendritic cells. J. Biol. Chem. 276:2001;37692-37699.
36. Hirschfeld M., Weis J.J., Toshchakov V., Salkowski C.A., Cody M.J., Ward D.C., Qureshi N., Michalek S.M., Vogel S.N. Signaling by Toll-like receptor 2 and 4 agonists results in differential gene expression in murine macrophages. Infect. Immun. 69:2001;1477-1482.
37. Jones B.W., Means T.K., Heldwein K.A., Keen M.A., Hill P.J., Belisle J.T., Fenton M.J. Different Toll-like receptor agonists induce distinct macrophage responses. J. Leukoc. Biol. 69:2001;1036-1044.
38. Supajatura V., Ushio H., Nakao A., Akira S., Okumura K., Ra C., Ogawa H. Differential responses of mast cell Toll-like receptors 2 and 4 in allergy and innate immunity. J. Clin. Invest. 109:2002;1351-1359.
39. Kawai T., Adachi O., Ogawa T., Takeda K., Akira S. Unresponsiveness of MyD88-deficient mice to endotoxin. Immunity. 11:1999;115-122.
40. Takeuchi O., Takeda K., Hoshino K., Adachi O., Ogawa T., Akira S. Cellular responses to bacterial cell wall components are mediated through MyD88-dependent signaling cascades. Int. Immunol. 12:2000;113-117.
41. Kawai T., Takeuchi O., Fujita T., Inoue J., Muhlradt P.F., Sato S., Hoshino K., Akira S. Lipopolysaccharide stimulates the MyD88-independent pathway and results in activation of IFN-regulatory factor 3 and the expression of a subset of lipopolysaccharide-inducible genes. J. Immunol. 167:2001;5887-5894 This paper shows that a MyD88-independent pathway activates IRF-3, with the subsequent induction of several IFN-inducible genes such as IP-10.
42. Toshchakov V., Jones B.W., Perera P.Y., Thomas K., Cody M.J., Zhang S., Williams B.R., Major J., Hamilton T.A., Fenton M.J.et al. TLR4, but not TLR2, mediates IFN-β-induced STAT1α/β-dependent gene expression in macrophages. Nat. Immunol. 3:2002;392-398 The authors show that TLR4 signaling, but not TLR2 signaling, induces IFN-β, thereby giving rise to secondary induction of IFN-inducible genes via activation of STAT1. This study also indicates that the adaptor molecule TIRAP (also known as Mal) is involved in the MyD88-independent pathway; however, this latter finding has been shown subsequently to be incorrect through the analysis of TIRAP knockout mice (M Yamamoto, K Takeda, S Akira, unpublished data; see Now in press).
43. Kaisho T., Takeuchi O., Kawai T., Hoshino K., Akira S. Endotoxin-induced maturation of MyD88-deficient dendritic cells. J. Immunol. 166:2001;5688-5694 It is shown that, in the absence of MyD88, DCs can mature in response to LPS in terms of the induction of co-stimulatory molecules and allogeneic T cell activation; however, MyD88-deficient DCs do not produce inflammatory cytokines.
44. ••].
45. ••] report the cloning of a novel adaptor molecule that specifically associates with the cytoplasmic portion of TLR4, and that may be a candidate adaptor involved in MyD88-independent pathway. But more recent studies of TIRAP knockout mice rule out this speculation and demonstrate the essential role of the protein in the MyD88-dependent pathway shared by TLR4 and TLR2 (M Yamamoto, K Takeda, S Akira, unpublished data; see Now in press).
46. Suzuki N., Suzuki S., Duncan G.S., Millar D.G., Wada T., Mirtsos C., Takada H., Wakeham A., Itie A., Li S.et al. Severe impairment of interleukin-1 and Toll-like receptor signalling in mice lacking IRAK-4. Nature. 416:2002;750-756 The phenotype of mice lacking a novel kinase, IRAK-4 is shown to be similar to that of MyD88 knockout mice. This kinase is essential to the host response to various pathogen components, such as LPS, CpG DNA and peptidoglycan.
47. Kobayashi K., Hernandez L.D., Galan J.E., Janeway C.A., Medzhitov R., Flavell R.A. IRAK-M is a negative regulator of Toll-like receptor signaling. Cell. 110:2002;191-202 This paper shows that IRAK-M acts as a negative regulator of TLR signaling, thereby differing from other IRAK family members, which are positive regulators in TLR signaling.
48. Haynes L.M., Moore D.D., Kurt-Jones E.A., Finberg R.W., Anderson L.J., Tripp R.A. Involvement of Toll-like receptor 4 in innate immunity to respiratory syncytial virus. J. Virol. 75:2001;10730-10737.
49. Rassa J.C., Meyers J.L., Zhang Y., Kudaravalli R., Ross S.R. Murine retroviruses activate B cells via interaction with Toll-like receptor 4. Proc. Natl. Acad. Sci. U.S.A. 99:2002;2281-2286.
50. Bowie A., Kiss-Toth E., Symons J.A., Smith G.L., Dower S.K., O'Neill L.A. A46R and A52R from vaccinia virus are antagonists of host IL-1 and Toll-like receptor signaling. Proc. Natl. Acad. Sci. U.S.A. 97:2000;10162-10167.
51. Kadowaki N., Ho S., Antonenko S., Malefyt R.W., Kastelein R.A., Bazan F., Liu Y.J. Subsets of human dendritic cell precursors express different Toll-like receptors and respond to different microbial antigens. J. Exp. Med. 194:2001;863-869.
52. Ito T., Amakawa R., Kaisho T., Hemmi H., Tajima K., Uehira K., Ozaki Y., Tomizawa H., Akira S., Fukuhara S. Interferon-α and interleukin-12 are induced differentially by Toll-like receptor 7 ligands in human blood dendritic cell subsets. J. Exp. Med. 195:2002;1507-1512.
53. Leadbetter E.A., Rifkin I.R., Hohlbaum A.M., Beaudette B.C., Shlomchik M.J., Marshak-Rothstein A. Chromatin-IgG complexes activate B cells by dual engagement of IgM and Toll-like receptors. Nature. 416:2002;603-607 The IgG/chromatin immune complex activates autoreactive B cells that express an antigen receptor specific for self-IgG through synergistic activation of the antigen-receptor-dependent and the MyD88-dependent signaling pathways. These findings suggest that TLR activation is involved in the pathogenesis of autoimmune diseases.
54. Yamamoto M, Sato S, Hemmi H, Sanjo H, Uematsu S, Kaisho T, Hoshino K, Takeuchi O, Kobayashi M, Fujita T et al.: Essential role of TIRAP/Mal for activation of the signaling cascade shared by TLR2 and TLR4. Nature 2002, in press.