Targeting of Toll-like receptors: a decade of progress in combating infectious diseases

Toll-like receptors (TLRs) recognise highly conserved molecular structures, collectively known as pathogen-associated molecular patterns. In the past two decades, development and clinical implementation of TLR ligands-ie, chemically modified synthetic derivatives of naturally occurring ligands and fully synthetic small molecules-have been topics of intense research. Targeted manipulation of TLR signalling has been applied clinically to boost vaccine effectiveness, promote a robust T helper 1-predominant immune response against viral infection, or dampen the exaggerated inflammatory response to bacterial infection. Use of these new therapeutic molecules as adjuncts to conventional pharmacotherapy or stand-alone treatments might offer solutions to unmet clinical needs or could replace existing partly effective therapeutic strategies.