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

Key Concept Ranking

Immune System Proteins
Bacterial Proteins
Cell Wall Components
Tumor Necrosis Factor
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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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Generic image for table
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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