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Mammals have an inherent capacity to recognize and respond to specific molecules of microbial origin, on a time scale of minutes following inoculation. A detailed understanding of precisely how recognition and response are mediated has stood as one of the principal goals of immunology.
Among the molecules recognized, lipopolysaccharide (LPS; endotoxin) has been most widely used to model infection, yet its receptor remained unknown until recently. We identified the receptor for LPS by positionally cloning a locus in mice (Lps) that governed LPS responses. The Lps locus was shown to encode Toll-like receptor 4, a homolog of the Drosophila Toll protein, which had been shown to have both developmental and immunological functions.
