LPS-TLR4 signaling to IRF-3/7 and NF-κB involves the toll adapters TRAM and TRIF

Journal of Experimental Medicine

Volumn 198, Issue 7, 2003, Pages 1043-1055

  Fitzgerald, Katherine A ^a   Rowe, Daniel C ^a   Barnes, Betsy J ^b   Caffrey, Daniel R ^c   Visintin, Alberto ^a   Latz, Eicke ^a   Monks, Brian ^a   Pitha, Paula M ^b   Golenbock, Douglas T ^a  

^a UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL   (United States)

^b JOHNS HOPKINS UNIVERSITY   (United States)

^c PFIZER INC   (United States)

Author keywords

Endotoxin; Host defense; Innate immunity; Interferon; Signal transduction

Indexed keywords

ADAPTOR PROTEIN; ALPHA INTERFERON; BETA INTERFERON; DIFFERENTIATION INDUCING FACTOR; ENDOTOXIN; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERFERON REGULATORY FACTOR 3; INTERLEUKIN 1; LIPOPOLYSACCHARIDE; MYELOID DIFFERENTIATION FACTOR 88; RANTES; TOLL LIKE RECEPTOR 4; UNCLASSIFIED DRUG;

ARTICLE; CELL MATURATION; ENHANCER REGION; HOST RESISTANCE; HUMAN; HUMAN CELL; IMMUNE RESPONSE; MOLECULAR CLONING; MUCOSAL IMMUNITY; PRIORITY JOURNAL; PROMOTER REGION; PROTEIN EXPRESSION; SIGNAL TRANSDUCTION; T LYMPHOCYTE ACTIVATION;

ADAPTOR PROTEINS, VESICULAR TRANSPORT; AMINO ACID SEQUENCE; ANIMALS; CELL LINE; DNA-BINDING PROTEINS; HUMANS; INTERFERON REGULATORY FACTOR-3; INTERFERON REGULATORY FACTOR-7; LIPOPOLYSACCHARIDES; MEMBRANE GLYCOPROTEINS; MICE; MICE, INBRED C57BL; MOLECULAR SEQUENCE DATA; NF-KAPPA B; RANTES; RECEPTORS, CELL SURFACE; RNA, DOUBLE-STRANDED; RNA, SMALL INTERFERING; SIGNAL TRANSDUCTION; TOLL-LIKE RECEPTOR 3; TOLL-LIKE RECEPTOR 4; TOLL-LIKE RECEPTORS; TRANSCRIPTION FACTORS;

EID: 0141959224     PISSN: 00221007     EISSN: None     Source Type: Journal    
DOI: 10.1084/jem.20031023     Document Type: Article

References (61)

1. Medzhitov, R., P. Preston-Hurlburt, and C.A. Janeway, Jr. 1997. A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature. 388:394-397.
2. Akira, S. 2001. Toll-like receptors and innate immunity. Adv. Immunol. 78:1-56.
3. Dunne, A., and L.A. O'Neill. 2003. The interleukin-1 receptor/Toll-like receptor superfamily: signal transduction during inflammation and host defense. Sci. STKE. 2003:re3.
4. Muzio, M., J. Ni, P. Feng, and V.M. Dixit. 1997. IRAK (Pelle) family member IRAK-2 and MyD88 as proximal mediators of IL- 1 signaling. Science. 278:1612-1615.
5. Janssens, S., and R. Beyaert. 2002. A universal role for MyD88 in TLR/IL-1R-mediated signaling. Trends Biochem. Sci. 27:474-482.
6. Cao, Z., W.J. Henzel, and X. Gao. 1996. IRAK: a kinase associated with the interleukin-1 receptor. Science. 271:1128-1131.
7. Li, S., A. Strelow, E.J. Fontana, and H. Wesche. 2002. IRAK-4: a novel member of the IRAK family with the properties of an IRAK-kinase. Proc. Natl. Acad. Sci. USA. 99:5567-5572.
8. Cao, Z., J. Xiong, M. Takeuchi, T. Kurama, and D.V. Goeddel. 1996. TRAF6 is a signal transducer for interleukin-1. Nature. 383:443-446.
9. Karin, M., and Y. Ben-Neriah. 2000. Phosphorylation meets ubiquitination: the control of NF-[kappa]B activity. Annu. Rev. Immunol. 18:621-663.
10. Kaisho, T., O. Takeuchi, T. Kawai, K. Hoshino, and S. Akira. 2001. Endotoxin-induced maturation of MyD88-deficient dendritic cells. J. Immunol. 166:5688-5694.
11. Kawai, T., O. Adachi, T. Ogawa, K. Takeda, and S. Akira. 1999. Unresponsiveness of MyD88-deficient mice to endotoxin. Immunity. 11:115-122.
12. Toshchakov, V., B.W. Jones, P.Y. Perera, K. Thomas, M.J. Cody, S. Zhang, B.K. Williams, J. Major, T.A. Hamilton, M.J. Fenton, and S.N. Vogel. 2002. TLR4, but not TLR2, mediates IFN-beta-induced STAT1alpha/beta-dependent gene expression in macrophages. Nat. Immunol. 3:392-398.
13. Oshiumi, H., M. Matsumoto, K. Funami, T. Akazawa, and T. Seya. 2003. TICAM-1, an adaptor molecule that participates in Toll-like receptor 3-mediated interferon-beta induction. Nat. Immunol. 4:161-167.
14. Kaisho, T., and S. Akira. 2001. Dendritic-cell function in Toll-like receptor- and MyD88-knockout mice. Trends Immunol. 22:78-83.
15. Kawai, T., O. Takeuchi, T. Fujita, J. Inoue, P.F. Muhlradt, S. Sato, K. Hoshino, and S. Akira. 2001. 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. 167:5887-5894.
16. Yamamoto, M., S. Sato, K. Mori, K. Hoshino, O. Takeuchi, K. Takeda, and S. Akira. 2002. Cutting edge: a novel Toll/IL-1 receptor domain-containing adapter that preferentially activates the IFN-beta promoter in the toll-like receptor signaling. J. Immunol. 169:6668-6672.
17. Doyle, S., S. Vaidya, R. O'Connell, H. Dadgostar, P. Dempsey, T. Wu, G. Rao, R. Sun, M. Haberland, R. Modlin, and G. Cheng. 2002. IRF3 mediates a TLR3/TLR4-specific antiviral gene program. Immunity. 17:251-263.
18. Fitzgerald, K.A., E.M. Palsson-McDermott, A.G. Bowie, C.A. Jefferies, A.S. Mansell, G. Brady, E. Brint, A. Dunne, P. Gray, M.T. Harte, et al. 2001. Mal (MyD88-adapter-like) is required for Toll-like receptor-4 signal transduction. Nature. 413:78-83.
19. Horng, T., G.M. Barton, and R. Medzhitov. 2001. TIRAP: an adapter molecule in the Toll signaling pathway. Nat. Immunol. 2:835-841.
20. Shinobu, N., T. Iwamura, M. Yoneyama, K. Yamaguchi, W. Suhara, Y. Fukuhara, F. Amano, and T. Fujita. 2002. Involvement of TIRAP/MAL in signaling for the activation of interferon regulatory factor 3 by lipopolysaccharide. FEBS Lett. 517:251-256.
21. Horng, T., G.M. Barton, R.A. Flavell, and R. Medzhitov. 2002. The adaptor molecule TIRAP provides signalling specificity for Toll-like receptors. Nature. 420:329-333.
22. Yamamoto, M., S. Sato, H. Hemmi, H. Sanjo, S. Uematsu, T. Kaisho, K. Hoshino, O. Takeuchi, M. Kobayashi, T. Fujita, et al. 2002. Essential role for TIRAP in activation of the signalling cascade shared by TLR2 and TLR4. Nature. 420:324-329.
23. Hiscott, J., P. Pitha, P. Genin, H. Nguyen, C. Heylbroeck, Y. Mamane, M. Algarte, and R. Lin. 1999. Triggering the interferon response: the role of IRF-3 transcription factor. J. Interferon Cytokine Res. 19:1-13.
24. Juang, Y.T., W. Lowther, M. Kellum, W.C. Au, R. Lin, J. Hiscott, and P.M. Pitha. 1998. Primary activation of interferon A and interferon B gene transcription by interferon regulatory factor 3. Proc. Natl. Acad. Sci. USA. 95:9837-9842.
25. Juang, Y.T., W.C. Au, W. Lowther, J. Hiscott, and P.M. Pitha. 1999. Lipopolysaccharide inhibits virus-mediated induction of interferon genes by disruption of nuclear transport of interferon regulatory factors 3 and 7. J. Biol. Chem. 274:18060-18066.
26. Lin, R., C. Heylbroeck, P. Genin, P.M. Pitha, and J. Hiscott. 1999. Essential role of interferon regulatory factor 3 in direct activation of RANTES chemokine transcription. Mol. Cell. Biol. 19:959-966.
27. Genin, P., M. Algarte, P. Roof, R. Lin, and J. Hiscott. 2000. Regulation of RANTES chemokine gene expression requires cooperativity between NF-kappa B and IFN-regulatory factor transcription factors. J. Immunol. 164:5352-5361.
28. Guo, J., K.L. Peters, and G.C. Sen. 2000. Induction of the human protein P56 by interferon, double-stranded RNA, or virus infection. Virology. 267:209-219.
29. Yoneyama, M., W. Suhara, and T. Fujita. 2002. Control of IRF-3 activation by phosphorylation. J. Interferon Cytokine Res. 22:73-76.
30. Servant, M.J., B. ten Oever, C. LePage, L. Conti, S. Gessani, I. Julkunen, R. Lin, and J. Hiscott. 2001. Identification of distinct signaling pathways leading to the phosphorylation of interferon regulatory factor 3. J. Biol. Chem. 276:355-363.
31. Wathelet, M.G., C.H. Lin, B.S. Parekh, L.V. Ronco, P.M. Howley, and T. Maniatis. 1998. Virus infection induces the assembly of coordinately activated transcription factors on the IFN-beta enhancer in vivo. Mol. Cell. 1:507-518.
32. Lin, R., C. Heylbroeck, P.M. Pitha, and J. Hiscott. 1998. Virus-dependent phosphorylation of the IRF-3 transcription factor regulates nuclear translocation, transactivation potential, and proteasome-mediated degradation. Mol. Cell. Biol. 18:2986-2996.
33. Yoneyama, M., W. Suhara, Y. Fukuhara, M. Fukuda, E. Nishida, and T. Fujita. 1998. Direct triggering of the type I interferon system by virus infection: activation of a transcription factor complex containing IRF-3 and CBP/p300. EMBO J. 17:1087-1095.
34. Weaver, B.K., K.P. Kumar, and N.C. Reich. 1998. Interferon regulatory factor 3 and CREB-binding protein/p300 are subunits of double-stranded RNA-activated transcription factor DKAF1. Mol. Cell. Biol. 18:1359-1368.
35. Au, W.C., P.A. Moore, D.W. LaFleur, B. Tombal, and P.M. Pitha. 1998. Characterization of the interferon regulatory factor-7 and its potential role in the transcription activation of interferon A genes. J. Biol. Chem. 273:29210-29217.
36. Yeow, W.S., W.C. Au, Y.T. Juang, C.D. Fields, C.L. Dent, D.R. Gewert, and P.M. Pitha. 2000. Reconstitution of virus-mediated expression of interferon alpha genes in human fibroblast cells by ectopic interferon regulatory factor-7. J. Biol. Chem. 275:6313-6320.
37. Marie, I., J.E. Durbin, and D.E. Levy. 1998. Differential viral induction of distinct interferon-alpha genes by positive feedback through interferon regulatory factor-7. EMBO J. 17:6660-6669.
38. Peters, R.T., S.M. Liao, and T. Maniatis. 2000. IKKepsilon is part of a novel PMA-inducible IkappaB kinase complex. Mol. Cell. 5:513-522.
39. Shimada, T., T. Kawai, K. Takeda, M. Matsumoto, J. Inoue, Y. Tatsumi, A. Kanamaru, and S. Akira. 1999. IKK-i, a novel lipopolysaccharide-inducible kinase that is related to IkappaB kinases. Int. Immunol. 11:1357-1362.
40. Pomerantz, J.L., and D. Baltimore. 1999. NF-kappaB activation by a signaling complex containing TRAF2, TANK and TBK1, a novel IKK-related kinase. EMBO J. 18:6694-6704.
41. Bonnard, M., C. Mirtsos, S. Suzuki, K. Graham, J. Huang, M. Ng, A. Itie, A. Wakeham, A. Shahinian, W.J. Henzel, et al. 2000. Deficiency of T2K leads to apoptotic liver degeneration and impaired NF-kappaB-dependent gene transcription. EMBO J. 19:4976-4985.
42. Tojima, Y., A. Fujimoto, M. Delhase, Y. Chen, S. Hatakeyama, K., Nakayama, Y. Kaneko, Y. Nimura, N. Motoyama, K. Ikeda, et al. 2000. NAK is an IkappaB kinase-activating kinase. Nature. 404:778-782.
43. Fitzgerald, K.A., S.M. McWhirter, K.L. Faia, D.C. Rowe, E. Latz, D.T. Golenbock, A.J. Coyle, S.M. Liao, and T. Maniatis. 2003. IKKepsilon and TBK1 are essential components of the IRF3 signaling pathway. Nat. Immunol. 4:491-496.
44. Sharma, S., B.R. tenOever, N. Grandvaux, G.P. Zhou, R. Lin, and J. Hiscott. 2003. Triggering the interferon antiviral response through an IKK-related pathway. Science. 300:1148-1151.
45. Sakaguchi, S., H. Negishi, M. Asagiri, C. Nakajima, T. Mizutani, A. Takaoka, K. Honda, and T. Taniguchi. 2003. Essential role of IRF-3 in lipopolysaccharide-induced interferon-beta gene expression and endotoxin shock. Biochem. Biophys. Res. Commun. 306:860-866.
46. Hirschfeld, M., Y. Ma, J.H. Weis, S.N. Vogel, and J.J. Weis. 2000. Cutting edge: repurification of lipopolysaccharide eliminates signaling through both human and murine toll-like receptor 2. J. Immunol. 165:618-622.
47. Latz, E., A. Visintin, E. Lien, K.A. Fitzgerald, B.G. Monks, E.A. Kurt-Jones, D.T. Golenbock, and T. Espevik. 2002. Lipopolysaccharide rapidly traffics to and from the Golgi apparatus with the toll-like receptor 4-MD-2-CD14 complex in a process that is distinct from the initiation of signal transduction. J. Biol. Chem. 277:47834-47843.
48. Visintin, A., A. Mazzoni, J.A. Spitzer, and D.M. Segal. 2001. Secreted MD-2 is a large polymeric protein that efficiently confers lipopolysaccharide sensitivity to Toll-like receptor 4. Proc. Natl. Acad. Sci. USA. 98:12156-12161.
49. Lien, E., J.C. Chow, L.D. Hawkins, P.D. McGuinness, K. Miyake, T. Espevik, F. Gusovsky, and D.T. Golenbock. 2001. A novel synthetic acyclic lipid A-like agonist activates cells via the lipopolysaccharide/toll-like receptor 4 signaling pathway. J. Biol. Chem. 276:1873-1880.
50. Fitzgerald, K.A., A.G. Bowie, B.S. Skeffington, and L.A. O'Neill. 2000. Ras, protein kinase C zeta, and I kappa B kinases 1 and 2 are downstream effectors of CD44 during the activation of NF-kappa B by hyaluronic acid fragments in T-24 carcinoma cells. J. Immunol. 164:2053-2063.
51. Alexopoulou, L., A.C. Holt, R. Medzhitov, and R.A. Flavell. 2001. Recognition of double-stranded RNA and activation of NF-kappaB by Toll-like receptor 3. Nature. 413:732-738.
52. Takeuchi, O., K. Takeda, K. Hoshino, O. Adachi, T. Ogawa, and S. Akira. 2000. Cellular responses to bacterial cell wall components are mediated through MyD88-dependent signaling cascades. Int. Immunol. 12:113-117.
53. Maniatis, T., J.V. Falvo, T.H. Kim, T.K. Kim, C.H. Lin, B.S. Parekh, and M.G. Wathelet. 1998. Structure and function of the interferon-beta enhanceosome. Cold Spring Harb. Symp. Quant. Biol. 63:609-620.
54. Xu, Y., X. Tao, B. Shen, T. Horng, R. Medzhitov, J.L. Manley, and L. Tong. 2000. Structural basis for signal transduction by the Toll/interleukin-1 receptor domains. Nature. 408:111-115.
55. Poltorak, A., X. He, I. Smirnova, M.Y. Liu, C.V. Huffel, X. Du, D. Birdwell, E. Alejos, M. Silva, C. Galanos, et al. 1998. Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science. 282:2085-2088.
56. Kravchenko, V.V., J.C. Mathison, K. Schwamborn, F. Mercurio, and R.J. Ulevitch. 2003. IKKi/IKKepsilon plays a key role in integrating signals induced by pro-inflammatory stimuli. J. Biol. Chem. 278:26612-26619.
57. Brummelkamp, T.R., R. Bernards, and R. Agami. 2002. A system for stable expression of short interfering RNAs in mammalian cells. Science. 296:550-553.
58. Doyle, S.E., R. O'Connell, S.A. Vaidya, E.K. Chow, K. Yee, and G. Cheng. 2003. Toll-like receptor 3 mediates a more potent antiviral response than Toll-like receptor 4. J. Immunol. 170:3565-3571.
59. Bin, L.H., L.G. Xu, and H.B. Shu. 2003. TIRP, a novel Toll/interleukin-1 receptor (TIR) domain-containing adapter protein involved in TIR signaling. J. Biol. Chem. 278:24526-24532.
60. Yamamoto, M., S. Sato, H. Hemmi, K. Hoshino, T. Kaisho, H. Sanjo, O. Takeuchi, M. Sugiyama, M. Okabe, K. Takeda, and S. Akira. 2003. Role of adaptor TRIF in the MyD88-independent toll-like receptor signaling pathway. Science. 301:640-643.
61. Hoebe, K., X. Du, P. Georgel, E. Janssen, K. Tabeta, S.O. Kim, J. Goode, P. Lin, N. Mann, S. Mudd, et al. 2003. Identification of Lps2 as a key transducer of MyD88-independent TIR signalling. Nature. 424:743-748.