Innate immune sensing of microbial infection: the mechanism and the therapeutic challenge.
Studies of sepsis conducted over the century have led to an understanding of many of the molecular events that take place during a severe infection. But what are the first events? Very recent genetic analyses have provided an answer to this question. Genetic studies have disclosed that bacterial endotoxin is sensed through a solitary biochemical pathway. At the heart of this pathway is the Toll-like receptor 4 (TLR4): one member of an ancient receptor family dedicated to the detection of infectious organisms. Most and perhaps all of the untoward effects of infection are initiated by the TLRs, ten of which are represented in humans. At the same time, it is known that TLRs are required to sense infection at its earliest stages, and thereby defeat it. The means to block TLR signal transduction is now at hand. Will this do good or harm?
Beutler
B
B
Scripps Research Institute, 10550 N. Torrey Pines Road, IMM-31, La Jolla, CA 92037, USA. bruce@scripps.edu
D000818:Animals; D001424:Bacterial Infections / Q000235:genetics / Q000276:immunology*; D029721:Drosophila Proteins; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000235:genetics; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000276:immunology; D008562:Membrane Glycoproteins / Q000235:genetics; D011956:Receptors, Cell Surface / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D013045:Species Specificity; D018746:Systemic Inflammatory Response Syndrome / Q000235:genetics / Q000276:immunology*; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
D029721:Drosophila Proteins; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors