Toll-like receptors in health and disease: complex questions remain

Until recently, the manner in which we respond to pathogens was obscure. It is now clear that a family of proteins, the Toll-like receptors (TLRs),3 contribute to the signal transduction induced by many pathogen-associated molecular patterns (PAMPs), and perhaps also to endogenous damage signals generated at sites of inflammation. Some TLRs act as central integrators of a wide variety of signals, responding to diverse agonists with an apparently common output, while other members of the family show (to date) considerable specificity with regard to their stimuli. However, many questions remain regarding the immunopharmacology of TLRs, their roles in innate immunity, and their manipulation by pathogens.