Chapter 12 : Toll/Interleukin-1 Receptors and Innate Immunity

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Innate immunity represents the sole mechanism of host defense against microbial infections in invertebrates. In mammals and other vertebrates, innate immunity provides the first line of host defense against these infections. Studies over the past few years have shown that Toll-like receptors (TLRs) are crucial molecules in the recognition of various pathogen-associatedmolecular patterns (PAMPs), and therefore represent a class of pattern-recognition receptors (PRRs). Like the TLRs, interleukin-1 receptor superfamily (IL-1Rs) also plays key roles in host responses to infection and inflammation. This chapter describes the current state of knowledge of these two superfamilies of receptors and their ligands, as well as the molecules that mediate the membrane-proximal events of their signaling. The intracellular region of Toll contains two domains (Fig. 1). The first, membraneproximal domain has about 150 residues and bears sequence homology to the intracellular domain of the IL-1 receptor (IL-1R). This domain is known as the TIR domain and is discussed in more detail. Many molecules have been identified in the signaling pathways of the IL-1Rs and TLRs. The chapter focuses on the membrane-proximal events of these pathways. The signal transduction through the TLRs and the IL-1Rs ultimately leads to the activation of the transcription factor NF-kB, the mitogenactivated protein (MAP) kinases (ERK, p38, and JNK) and transcription factors of the AP-1 family. Structural biology is the most important experimental technique for addressing issues regarding the molecular basis of innate immunity.

Citation: Tong L. 2005. Toll/Interleukin-1 Receptors and Innate Immunity, p 241-263. In Waksman G, Caparon M, Hultgren S (ed), Structural Biology of Bacterial Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/9781555818395.ch12
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Image of Figure 1.
Figure 1.

Domain organization of TLRs, IL-1Rs, and associated molecules. The individual domains are indicated by the shapes of their symbols. For all the proteins, the N terminus is on the left.

Citation: Tong L. 2005. Toll/Interleukin-1 Receptors and Innate Immunity, p 241-263. In Waksman G, Caparon M, Hultgren S (ed), Structural Biology of Bacterial Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/9781555818395.ch12
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Image of Figure 2.
Figure 2.

Signaling pathways for TLRs and IL-1Rs. (A) Membrane-proximal events in the signal transduction. The TIR domains are shown as solid rectangles, and the death domains are shown as solid circles. (B) Overall signaling events in the TLR and IL-1R pathways. Abbreviations: TRAF, TNF-α receptor-associated factor; TAK, transforming growth factor β- activated kinase;MKK,MAPkinase kinase; IKK, I-?B kinase;TBK,TANK-binding kinase.

Citation: Tong L. 2005. Toll/Interleukin-1 Receptors and Innate Immunity, p 241-263. In Waksman G, Caparon M, Hultgren S (ed), Structural Biology of Bacterial Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/9781555818395.ch12
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1. Aderem, A.,, and R. J. Ulevitch. 2000. Toll-like receptors in the induction of the innate immune response. Nature 406: 782 787.
2. Anderson, K. V. 2000. Toll signaling pathways in the innate immune response. Curr. Opin. Immunol. 12: 13 19.
3. Arbibe, L.,, J.-P. Mira,, N. Teusch,, L. Kline,, M. Guha,, N. Mackman,, P. J. Godowski,, R. J. Ulevitch,, and U. G. Knaus. 2000. Toll-like receptor2-mediated NF-κB activation requires a Rac1-dependent pathway. Nat. Immunol. 1: 533 540.
4. Asai, T.,, G. Tena,, J. Plotnikova,, M. R. Willmann,, W.-L. Chiu,, L. Gomez-Gomez,, T. Boller,, F. M. Ausubel,, and J. Sheen. 2002. MAP kinase signalling cascade in Arabidopsis innate immunity. Nature 415: 977 983.
5. Bahi, N.,, G. Friocourt,, A. Carrie,, M. E. Graham,, J. L. Weiss,, P. Chafey,, F. Fauchereau,, R. D. Burgoyne,, and J. Chelly. 2003. IL1 receptor accessory protein like, a protein involved in X-linked mental retardation, interacts with neuronal calcium sensor-1 and regulates exocytosis. Human Mol. Gen. 12: 1415 1425.
6. Beutler, B. 2000. Tlr4: central component of the sole mammalian LPS sensor. Curr. Opin. Immunol. 12: 20 26.
7. Beutler, B.,, and H. Wagner (ed.) 2002. Toll-Like Receptor Family Members and Their Ligands. Springer-Verlag KG, Berlin, Germany.
8. Bin, L.-H.,, L.-G. Xu,, and H.-B. Shu. 2003. TIRP: a novel Toll/interleukin-1 receptor (TIR) domain containing adaptor protein involved in TIR signaling. J. Biol. Chem. 278: 24526 24532.
9. Brint, E. K.,, K. A. Fitzgerald,, P. Smith,, A. J. Coyle,, J.-C. Gutierrez-Ramos,, P. G. Fallon,, and L. A. J. O’Neill. 2002. Characterization of signaling pathways activated by the interleukin 1 (IL-1) receptor homologue T1/ST2. J. Biol. Chem. 277: 49205 49211.
10. Burns, K.,, S. Janssens,, B. Brissoni,, N. Olivos,, R. Beyaert,, and J. Tschopp. 2003. Inhibition of interleukin 1 receptor/Toll-like receptor signaling through the alternatively spliced, short form of MyD88 is due to its failure to recruit IRAK-4. J. Exp. Med. 197: 263 268.
11. Chamaillard, M.,, M. Hashimoto,, Y. Horie,, J. Masumoto,, S. Qiu,, L. Saab,, Y. Ogura,, A. Kawasaki,, K. Fukase,, S. Kusumoto,, M. A. Valvano,, S. J. Foster,, T. W. Mak,, G. Nunez,, and N. Inohara. 2003. An essential role for NOD1 in host recognition of bacterial peptidoglycan containing diaminopomelic acid. Nat. Immunol. 4: 702 707.
12. Dunne, A.,, and L. A. J. O’Neill. 2003. The interleukin-1 recepor/Toll-like receptor superfamily: signal transduction during inflammation and host defense. Sci. STKE 2003: re3.
13. Girardin, S. E.,, I. G. Boneca,, L. A. M. Carneiro,, A. Antignac,, M. Jehanno,, J. Viala,, K. Tedin,, M.-K. Taha,, A. Labigne,, U. Zahringer,, A. J. Coyle,, P. S. DiStefano,, J. Bertin,, P. J. Sansonetti,, and D. J. Philpott. 2003. Nod1 detects a unique muropeptide from Gram-negative bacterial peptidoglycan. Science 300: 1584 1587.
14. Grosshans, J.,, F. Schnorrer,, and C. Nusslein-Volhard. 1999. Oligomerization of Tube and Pelle leads to nuclear localisation of Dorsal. Mech. Dev. 81: 127 138.
15. Hajjar, A. M.,, R. K. Ernst,, J. H. Tsai,, C. B. Wilson,, and S. I. Miller. 2002. Human Toll-like receptor 4 recognizes host-specific LPS modifications. Nat. Immunol. 3: 354 359.
16. Hoebe, K.,, K. Du,, P. Georgel,, E. Janssen,, K. Tabeta,, S. O. Kim,, J. Goode,, P. Lin,, N. Mann,, S. Mudd,, K. Crozat,, S. Sovath,, J. Han,, and B. Beutler. 2003. Identification of Lps2 as a key transducer of MyD88- independent TIR signalling. Nature 424: 743 748.
17. Hoffmann, J. A.,, F. C. Kafatos,, C. A. Janeway, Jr.,., and R. A. B. Ezekowitz. 1999. Phylogenetic perspectives in innate immunity. Science 284: 1313 1318.
18. Janeway, C. A., Jr. 1989. Approaching the asymptote? Evolution and revolution in immunology. Cold Spring Harbor Symp. Quant. Biol. LIV: 1 13.
19. Jensen, L. E.,, and A. S. Whitehead. 2003. Pellino 2 activates the mitogen activated protein kinase pathway. FEBS Lett. 545: 199 202.
20. Jiang, Z.,, H. J. Johnson,, H. Nie,, J. Qin,, T. A. Bird,, and X. Li. 2003. Pellino 1 is required for interleukin-1 (IL-1)-mediated signaling through its interaction with the IL-1 receptor-associated kinase 4 (IRAK4)-IRAKtumor necrosis factor receptor-associated factor 6 (TRAF6) complex. J. Biol. Chem. 278: 10952 10956.
21. Koh, P. O.,, A. S. Undie,, N. Kabbani,, R. Levenson,, P. S. Goldman-Rakic,, and M. S. Lidow. 2003. Upregulation of neuronal calcium sensor-1 (NCS-1) in the prefrontal cortex of schizophrenic and bipolar patients. Proc. Natl. Acad. Sci. USA 100: 313 317.
22. Marmiroli, S.,, A. Bavelloni,, I. Faenza,, A. Sirri,, A. Ognibene,, V. Cenni,, J. Tsukada,, Y. Koyama,, M. Ruzzene,, A. Ferri,, P. E. Auron,, A. Toker,, and N. M. Maraldi. 1998. Phosphotidylinositol 3-kinase is recruited to a specific site in the activated IL-1 receptor 1. FEBS Lett. 438: 49 54.
23. Medzhitov, R.,, and C. A. Janeway, Jr. 1997. Innate immunity: the virtues of a nonclonal system of recognition. Cell 91: 295 298.
24. Meyers, B. C.,, A. Kozik,, A. Griego,, H. Kuang,, and R. W. Michelmore. 2003. Genome-wide analysis of NBSLRR- encoding genes in Arabidopsis. Plant Cell 15: 809 834.
25. O’Neill, L. A. J. 2003. The role of MyD88-like adaptors in Toll-like receptor signal transduction. Biochem. Soc. Trans. 31: 643 647.
26. Pereira, J. P.,, R. Girard,, R. Chaby,, A. Cumano,, and P. Vieira. 2003. Monoallelic expression of the murine gene encoding Toll-like receptor 4. Nat. Immunol. 4: 464 470.
27. Shen, B.,, and J. L. Manley. 1998. Phosphorylation modulates direct interactions between the Toll receptor, Pelle kinase and Tube. Development 125: 4719 4728.
28. Sims, J. E. 2002. IL-1 and IL-18 receptors, and their extended family. Curr. Opin. Immunol. 14: 117 122.
29. Sing, A.,, D. Rost,, N. Tvardovskaia,, A. Roggenkamp,, A. Wiedemann,, C. J. Kirschning,, M. Aepfelbacher,, and J. Heesemann. 2002. Yersinia V-antigen exploits Toll-like receptor 2 and CD14 for interleukin 10-mediated immunosupression. J. Exp. Med. 196: 1017 1024.
30. Sun, H.,, B. N. Bristow,, G. Qu,, and S. A. Wasserman. 2002. A heterotrimeric death domain complex in Toll signaling. Proc. Natl. Acad. Sci. USA 99: 12871 12876.
31. Takeda, K.,, and S. Akira. 2003. Toll receptors and pathogen resistance. Cell. Microbiol. 5: 143 153.
32. Tschopp, J.,, F. Martinon,, and K. Burns. 2003. NALPs: a novel protein family involved in inflammation. Nat. Rev. Mol. Cell Biol. 4: 95 104.
33. Underhill, D. M.,, and A. Ozinsky. 2002. Toll-like receptors: key mediators of microbe detection. Curr. Opin. Immunol. 14: 103 110.
34. Wald, D.,, J. Qin,, Z. Zhao,, Y. Qian,, M. Naramura,, L. Tian,, J. Towne,, J. E. Sims,, G. Stark,, and X. Li. 2003. SIGIRR, a negative regulator of Toll-like receptor-interleukin 1 receptor signaling. Nat. Immunol. 4: 920 927.
35. Weber, A. N. R.,, S. Tauszig-Delamasure,, J. A. Hoffmann,, E. Lelievre,, H. Gascan,, K. P. Ray,, M. A. Morse,, J. L. Imler,, and N. J. Gay. 2003. Binding of the Drosophila cytokine Spatzle to Toll is direct and establishes signaling. Nat. Immunol. 4: 794 800.
36. 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.
37. Yu, K.-Y.,, H.-J. Kwon,, D. A. M. Norman,, E. Vig,, M. G. Goebl,, and M. A. Harrington. 2002. Mouse Pellino-2 modulates IL-1 and lipopolysaccharide signaling. J. Immunol. 169: 4075 4078.


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Table 1.

IL-1 receptors and TLRs

Citation: Tong L. 2005. Toll/Interleukin-1 Receptors and Innate Immunity, p 241-263. In Waksman G, Caparon M, Hultgren S (ed), Structural Biology of Bacterial Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/9781555818395.ch12

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