The Toll-like receptors: Analysis by forward genetic methods

Research output: Contribution to journalArticle

96 Citations (Scopus)

Abstract

Many genes, and conceivably most genes, are constitutively expressed yet have conditional functions. Their products are utilized only under special circumstances, and enforce homeostatic regulation. Mutations do not disclose the function of such genes unless the proper conditions are applied. The genes that encode the Toll-like receptors (TLRs) fall into this category. The TLRs represent the principal sensors of infection in mammals. Absent infection, mammals have little need for the TLRs; they are essential only when microbes gain access to the interior milieu of the host. The function of the TLRs in mammals was first disclosed by a spontaneous mutation in a locus called Lps, when it was shown by positional cloning to be identical to Tlr4. Random germline mutagenesis has since permitted an estimate of the total number of proteins required for TLR signaling to the level of tumor necrosis factor (TNF) synthesis and activity, and has also shown that these sensors are extremely broad in their ability to detect microbes. Ultimately, the TLRs are responsible for most infection-related phenomena, both good and bad. These include the development of fever, shock, and tissue injury, but also the activation of innate and adaptive effector mechanisms that lead to the elimination of microbes.

Original languageEnglish (US)
Pages (from-to)385-392
Number of pages8
JournalImmunogenetics
Volume57
Issue number6
DOIs
StatePublished - Jul 2005

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Toll-Like Receptors
Mammals
Genes
Infection
Mutation
Mutagenesis
Organism Cloning
Shock
Fever
Tumor Necrosis Factor-alpha
Wounds and Injuries
Proteins

Keywords

  • Genetics
  • Host resistance
  • Innate immunity
  • Mutagenesis
  • TLR
  • Toll-like receptor

ASJC Scopus subject areas

  • Immunology
  • Genetics

Cite this

The Toll-like receptors : Analysis by forward genetic methods. / Beutler, Bruce.

In: Immunogenetics, Vol. 57, No. 6, 07.2005, p. 385-392.

Research output: Contribution to journalArticle

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