Abstract
The innate immune system forms the first line of defense against pathogens. The Toll-like receptors and the Nod-like receptors are at the forefront of both extracellular and intracellular pathogen recognition. They recognize the most conserved structures of microbes and initiate the response to infection. In addition to the microbial stimuli, they are now also being implicated in the recognition of danger-associated stimuli, making them pivotal in disorders unrelated to microbial pathogenesis. Toll-like receptors and the Nod-like receptors share commonalities in structure, ligands and downstream signalling but they differ in their localization, and extent of influence on a wide variety of cellular processes including apoptosis. Here we discuss the common ligand recognition and signalling modules in both these classes of receptors.
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References
Medzhitov R, Preston-Hurlburt P, Janeway Jr CA. A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature 1997; 388:394–397.
Rock FL, Hardiman G, Timans JC et al. A family of human receptors structurally related to Drosophila Toll. Proc Natl Acad Sci USA 1998; 95:588–593.
Matsuguchi T, Takagi K, Musikacharoen T et al. Gene expressions of lipopolysaccharide receptors, toll-like receptors 2 and 4, are differently regulated in mouse T lymphocytes. Blood 2000; 95:1378–1385.
Takeda K, Akira S. Toll-like receptors in innate immunity. Int Immunol 2005; 17:1–14.
Armant MA, Fenton MJ. Toll-like receptors: A family of pattern-recognition receptors in mammals. Genome Biol 2002; 3:REVIEWS3011.
Takeuchi O, Sato S, Horiuchi T et al. Cutting edge: Role of Toll-like receptor 1 in mediating immune response to microbial lipoproteins. J Immunol 2002; 169:10–14.
Okamura Y, Watari M, Jerud ES et al. The extra domain A of fibronectin activates Toll-like receptor 4. J Biol Chem 2001; 276:10229–10233.
Sasu S, LaVerda D, Qureshi N et al. Chlamydia pneumoniae and chlamydial heat shock protein 60 stimulate proliferation of human vascular smooth muscle cells via toll-like receptor 4 and p44/ p42 mitogen-activated protein kinase activation. Circ Res 2001; 89:244–250.
Basu S, Fenton MJ. Toll-like receptors: Function and roles in lung disease. Am J Physiol Lung Cell Mol Physiol 2004; 286:L887–L892.
Ben Ali M, Barbouche MR, Bousnina S et al. Toll-like receptor 2 Arg677Trp polymorphism is associated with susceptibility to tuberculosis in Tunisian patients. Clin Diagn Lab Immunol 2004; 11:625–626.
Berdeli A, Celik HA, Ozyurek R et al. TLR-2 gene Arg753Gln polymorphism is strongly associated with acute rheumatic fever in children. J Mol Med 2005; 83:535–541.
Bihl F, Lariviere L, Qureshi ST et al. LPS-hyporesponsiveness of mnd mice is associated with a mutation in Toll-like receptor 4. Genes Immun 2001; 2:56–59.
Franchimont D, Vermeire S, El Housni H et al. Deficient host-bacteria interactions in inflammatory bowel disease? The toll-like receptor (TLR)-4 Asp299gly polymorphism is associated with Crohn’ s disease and ulcerative colitis. Gut 2004; 53:987–992.
Hawn TR, Verbon A, Lettinga KD et al. A common dominant TLR5 stop codon polymorphism abolishes flagellin signaling and is associated with susceptibility to legionnaires’ disease. J Exp Med 2003; 198:1563–1572.
Mockenhaupt FP, Cramer JP, Hamann L et al. Toll-like receptor (TLR) polymorphisms in African children: Common TLR-4 variants predispose to severe malaria. Proc Natl Acad Sci USA 2006; 103:177–182.
Montes AH, Asensi V, Alvarez V et al. The Toll-like receptor 4 (Asp299Gly) polymorphism is a risk factor for Gram-negative and haematogenous osteomyelitis. Clin Exp Immunol 2006; 143:404–413.
Conti BJ, Davis BK, Zhang J et al. CATERPILLER 16.2 (CLR16.2), a novel NBD/LRR family member that negatively regulates T cell function. J Biol Chem 2005; 280:18375–18385.
Girardin SE, Sansonetti PJ, Philpott DJ. Intracellular vs extracellular recognition of pathogens — common concepts in mammals and flies. Trends Microbiol 2002; 10:193–199.
Ting JP, Kastner DL, Hoffman HM. CATERPILLERs, pyrin and hereditary immunological disorders. Nat Rev Immunol 2006; 6:183–195.
Martinon F, Tschopp J. NLRs join TLRs as innate sensors of pathogens. Trends Immunol 2005; 26:447–454.
Inohara, Chamaillard, McDonald C et al. NOD-LRR proteins: Role in host-microbial interactions and inflammatory disease. Annu Rev Biochem 2005; 74:355–383.
Chin KC, Li GG, Ting JP. Importance of acidic, proline/serine/threonine-rich, and GTP-binding regions in the major histocompatibility complex class II transactivator: Generation of transdominant-negative mutants. Proc Natl Acad Sci USA 1997; 94:2501–2506.
Fairbrother WJ, Gordon NC, Humke EW et al. The PYRIN domain: A member of the death domain-fold superfamily. Protein Sci 2001; 10:1911–1918.
Chamaillard M, Girardin SE, Viala J et al. Intracellular regulators of bacterial-induced inflammation. Cell Microbiol 2003; 5:581–592.
Verhagen AM, Coulson EJ, Vaux DL. Inhibitor of apoptosis proteins and their relatives: IAPs and other BIRPs. Genome Biol 2001; 2:REVIEWS 3009.
Rosenstiel P, Till A, Schreiber S. NOD-like receptors and human diseases. Microbes Infect 2007; 5:648–657
Orrell RW, Habgood JJ, de Belleroche JS et al. The relationship of spinal muscular atrophy to motor neuron disease: Investigation of SMN and NAIP gene deletions in sporadic and familial ALS. J Neurol Sci 1997; 1:55–61.
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Langefeld, T., Mohamed, W., Ghai, R., Chakrabotty, T. (2009). Toll-like Receptors and NOD-Like Receptors: Domain Architecture and Cellular Signalling. In: Kishore, U. (eds) Target Pattern Recognition in Innate Immunity. Advances in Experimental Medicine and Biology, vol 653. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-0901-5_4
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DOI: https://doi.org/10.1007/978-1-4419-0901-5_4
Publisher Name: Springer, New York, NY
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