TLR4 as the mammalian endotoxin sensor

Research output: Contribution to journalArticle

165 Citations (Scopus)

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 the Drosophila 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 in Mammalia, which to the present time is the only class of the phylum Chordata 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.

Original languageEnglish (US)
Pages (from-to)109-120
Number of pages12
JournalCurrent Topics in Microbiology and Immunology
Volume270
StatePublished - 2002

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Innate Immunity
Endotoxins
CD14 Antigens
Chordata
Gene Knockout Techniques
Toll-Like Receptor 4
Molecular Structure
Lipopolysaccharides
Organism Cloning
Mammals
Genes
Drosophila Tl protein

ASJC Scopus subject areas

  • Immunology and Allergy
  • Microbiology (medical)
  • Immunology and Microbiology(all)
  • Microbiology

Cite this

TLR4 as the mammalian endotoxin sensor. / Beutler, Bruce.

In: Current Topics in Microbiology and Immunology, Vol. 270, 2002, p. 109-120.

Research output: Contribution to journalArticle

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