Toll-like receptors: a family of innate sensors of danger that alert and drive immunity

The innate immune system possesses a network of germline-encoded receptors that recognize microbial molecular motifs and endogenous molecules produced by injured tissues and set in motion a defensive response which adapts to the damage that has occurred. This network includes Toll-like receptors (TLRs), a family of transmembrane receptors that recognize a wide spectrum of ligands at the cell surface and in the lumen of intracellular vesicles. Recognition of ligands by TLRs induces the recruitment of different cytoplasmic adaptor molecules and initiates signalling pathways which ultimately lead to the activation of transcriptional factors such as NF-kappa B, IRF1/3/5/7, or AP-1. These factors are involved in the expression of inflammatory cytokines, chemokines, type 1 interferons, co-stimulatory molecules, and other factors of the effector response. TLRs regulate many aspects of both innate and adaptive immunity. To prevent an inappropriate or an overactive immune response, a complex network of molecules negatively regulates TLRs and their associated signalling pathways. TLRs are currently viewd as important targets for the development of new vaccines and innovative therapies which may help prevent or treat disorders such as cancer, allergy, autoimmunity, obesity, atherosclerosis, and other inflammatory diseases.