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?