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The Toll-like receptors: analysis by forward genetic methods

Content Provider	Springer Nature Link
Author	Beutler, Bruce
Copyright Year	2005
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.
Starting Page	385
Ending Page	392
Page Count	8
File Format	PDF
ISSN	00937711
Journal	Immunogenetics
Volume Number	57
Issue Number	6
e-ISSN	14321211
Language	English
Publisher	Springer-Verlag
Publisher Date	2005-07-02
Publisher Place	Berlin, Heidelberg
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	TLR Toll-like receptor Innate immunity Host resistance Genetics Mutagenesis Cell Biology Allergology Immunology
Content Type	Text
Resource Type	Article
Subject	Genetics Immunology

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