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Innate immune sensing and its roots: the story of endotoxin

Nature Reviews Immunology volume 3, pages 169–176 (2003)Cite this article

Abstract

How does the host sense pathogens? Our present concepts grew directly from longstanding efforts to understand infectious disease: how microbes harm the host, what molecules are sensed and, ultimately, the nature of the receptors that the host uses. The discovery of the host sensors — the Toll-like receptors — was rooted in chemical, biological and genetic analyses that centred on a bacterial poison, termed endotoxin.

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Figure 1: Hippocrates and Galenos, the leading medical doctors of their times and creators of the theory that many diseases are of poisonous origin.
Figure 2: A Gram-negative bacterium.
Figure 3: LPS signalling.

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Acknowledgements

B.B. is supported by a grant from the National Institutes of Health and by a grant from the Defense Advanced Projects Research Agency (DARPA). E.Th.R. is supported by the Deutsche Forschungsgemeinschaft and the Fonds der Chemischen Industrie. We thank I. Bendt, C. Alexander and G. Müller for typing this manuscript and for photographical work. We further thank A. Neschke for help in translating the Latin text of Fig. 1. This article is dedicated to our colleague and friend Jack Levin, Editor-in-Chief of the Journal of Endotoxin Research, on the occasion of his 70th birthday (11 October 2002).

Author information

Authors and Affiliations

  1. The Scripps Research Institute, La Jolla, 92037, California, USA

    Bruce Beutler

  2. Research Center, Borstel, D-23845, Borstel, Germany

    Ernst Th. Rietschel

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  1. Bruce Beutler
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Correspondence to Bruce Beutler.

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DATABASES

LocusLink

CD14

IL-1

IL-18

MD2

MyD88

TLR1

TLR2

TLR3

TLR4

TLR5

TLR6

TLR7

TLR8

TLR9

TNF

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Beutler, B., Rietschel, E. Innate immune sensing and its roots: the story of endotoxin. Nat Rev Immunol 3, 169–176 (2003). https://doi.org/10.1038/nri1004

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