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TLR4 as the Mammalian Endotoxin Sensor

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Toll-Like Receptor Family Members and Their Ligands

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 270))

Abstract

For more than a century, the ability to sense endotoxin (later known also as lipopolysaccharide; LPS) stood as the archetypal innate immune response: even before the phrase ‘innate immunity’ became popular. Yet the mechanism by which LPS initiated a signal remained unknown. The problem was solved in 1998 by positional cloning, which revealed that Toll-like receptor (TLR) 4, one of ten mammalian paralogues with homology to theDrosophila protein Toll, is the central component of the LPS receptor. During the 3 years that followed, gene knockout work supported the view that the TLRs perceive a number of indispensable molecular structures shared by diverse representatives of the microbial world. The highly specific LPS-sensing function of TLR4 is remarkable for its prevalence inMammalia, which to the present time is the only class of the phylumChordata known to have a gene encoding TLR4, and known to display exquisite sensitivity to LPS. The fact that LPS signals are elicited through a single biochemical pathway has raised important pharmacotherapeutic opportunities as well.

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Authors and Affiliations

  1. Department of Immunology, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA, 92037, USA

    B. Beutler

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  1. B. Beutler
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Editors and Affiliations

  1. Department of Immunology, The Scripps Research Institute, 10550 N. Torreye Pines Road, 92037, La Jolla, California, USA

    Bruce Beutler M.D.

  2. Institut für Medizinische Mikrobiologie, Immunologie and Hygiene Technische Universität München, Trogerstr. 9, 81675, München, Germany

    Hermann Wagner

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© 2002 Springer-Verlag Berlin Heidelberg

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Beutler, B. (2002). TLR4 as the Mammalian Endotoxin Sensor. In: Beutler, B., Wagner, H. (eds) Toll-Like Receptor Family Members and Their Ligands. Current Topics in Microbiology and Immunology, vol 270. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-59430-4_7

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  • DOI: https://doi.org/10.1007/978-3-642-59430-4_7

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-63975-3

  • Online ISBN: 978-3-642-59430-4

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