Toll-like receptors: how they work and what they do.

The Toll-like receptors are the primary sensors of the innate immune system. This assignment of function was predicated on positional cloning, and was the result of long and painstaking inquiry into the mechanism of responses to bacterial endotoxin, the abundant lipopolysaccharide component of the outer membrane of Gram-negative bacteria. The sequence of events that led to the discovery of Toll-like receptor function carries an important lesson that should guide further analysis of the innate immune system.