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PMID: 16001129 Published · ppublish English Journal Article Review

The Toll-like receptors: analysis by forward genetic methods.

Immunogenetics ·Vol. 57 ·No. 6 ·2005-07-00 ·Pages 385-92

Beutler B

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.

MeSH Terms
Animals Evolution, Molecular Immunity, Innate Membrane Glycoproteins/genetics,physiology Receptors, Cell Surface/genetics,physiology Signal Transduction Toll-Like Receptor 4 Toll-Like Receptors
Chemicals
Membrane Glycoproteins Receptors, Cell Surface Toll-Like Receptor 4 Toll-Like Receptors
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Beutler Bruce
The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USA. Bruce@scripps.edu
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Article Info
Journal
Immunogenetics
Abbr.
Immunogenetics
ISSN
0093-7711
DOI
10.1007/s00251-005-0011-3
Email
bruce@scripps.edu
Published
2005-07-00
Pages
385-92
Language
English
Region
United States
NLM ID
0420404
Subset
IM
External Links
PubMed source DOI: 10.1007/s00251-005-0011-3 View journal details
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