TLR4 as the mammalian endotoxin sensor

Research output: Contribution to journalReview article

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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
DOIs
StatePublished - Jan 1 2002

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ASJC Scopus subject areas

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

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