Toll-like receptors as adjuvant receptors

The mammalian Toll-like receptors (TLRs) are expressed on macrophages and dendritic cells, which are primarily involved in innate immunity. At present, ligands for several of the TLRs, such as TLR2, TLR3, TLR4, TLR5, TLR6, and TLR9, have been identified. Most of these ligands are derived from pathogens, but not found in the host, suggesting that the TLRs are critical to sensing invading microorganisms. Pathogen recognition by TLRs provokes rapid activation of innate immunity by inducing production of proinflammatory cytokines and upregulation of costimulatory molecules. Activated innate immunity subsequently leads to effective adaptive immunity. In this regard, the TLRs are considered to be adjuvant receptors. Distinct TLRs can exert distinct, but overlapping sets of biological effects. Accumulating evidence indicates that this can be attributed to both the common and unique aspects of the signaling mechanisms that mediate TLR family responses. For example, TLR2 and TLR9 require MyD88 as an essential signal transducer, whereas TLR4 can induce costimulatory molecule upregulation in a MyD88-independent manner. Understanding the TLR system should offer invaluable opportunity for manipulating host immune responses.