Role of Toll-like receptors in infection and immunity: clinical implications

The remarkable discovery of the Toll-like receptors (TLRs) over the past 5 years has opened up an entirely new era in the understanding of the molecular events that initiate the inflammatory response. These type 1 transmembrane receptors are expressed on a large number of immune cells as well as epithelial cells and play an essential role in the activation of the innate immune response to microbial pathogens. They impact on adaptive immune reactions and contribute to the initiation and maintenance of the inflammatory response to a multitude of potential microbial pathogens through recognition of pathogen-associated molecular patterns. TLRs also interact with a variety of endogenous human ligands and influence the activity of a wide range of tissues and cell processes. Among the common and important processes in which TLRs play a role are asthma, acute respiratory distress syndrome, cardiac ischaemia, coronary artery disease, ventricular remodelling, vascular collapse, inflammatory bowel disease, acute tubular necrosis, psoriasis, rheumatoid arthritis, pre-term birth, fertility, cancer angiogenesis and transplant rejection. From this strikingly diverse list, many important opportunities for disease modification through TLR manipulation can be imagined. Their role as potential targets for therapeutic intervention is just beginning to be appreciated, and the current status of these treatment strategies is reviewed in this article.