Roles for accessory molecules in microbial recognition by Toll-like receptors

The Toll family of receptors recognizes a variety of microbial products and triggers immune responses. Recent progress has revealed a requirement for accessory molecules in microbial recognition by Toll-like receptors. Lipopolysaccharide (LPS) recognition requires LPS binding protein (LBP), CD14, and MD-2. MD-2 is directly involved in ligand-binding and subsequent receptor activation, whereas LBP and CD14 control ligand presentation to the receptor complex, Toll-like receptor (TLR4)/MD-2. CD14 and LBP influence the amplitude of LPS responses and LPS-induced type I interferon production. TLR2 is also reported to require similar accessory molecules. Innate immune responses to microbial products driven by TLRs are controlled by accessory molecules working upstream of TLRs.