ABSTRACT

In the last decade, extraordinary progress has been made in characterizing at

the molecular and genetic level the components of the human immune system

that mediate the innate response to microbial organisms and products.

Among these components are CD14 and the family of toll-like receptors (TLRs). CD14 interacts with TLR4 and at least another protein, MD-2, to

form a receptor complex with specificity for endotoxin [lipopolysaccharide,

(LPS)—a component of gram-negative bacteria]. The TLR family includes

at least 10 transmembrane proteins (TLR1-10) that recognize a large variety

of viral and bacterial constituents and are essential for an effective host

defense against microbes. The sequencing of the human genome has revealed

substantial interindividual variation in the genes encoding CD14 and TLRs,

and functional studies have shown that some of these genetic variants have a significant impact on gene expression and/or protein function (1).