Toll-like receptors (TLRs) play crucial roles in the innate immune system by recognizing pathogen-associated molecular patterns derived from various microbes. TLRs signal through the recruitment of specific adaptor molecules, leading to activation of the transcription factors NF-κB and IRFs, which dictate the outcome of innate immune responses. During the past decade, the precise mechanisms underlying TLR signalling have been clarified by various approaches involving genetic, biochemical, structural, cell biological, and bioinformatics studies. TLR signalling appears to be divergent and to play important roles in many aspects of the innate immune responses to given pathogens.
The innate immune system employs germline-encoded pattern-recognition receptors (PRRs) for the initial detection of microbes. PRRs recognize microbe-specific molecular signatures known as pathogen-associated molecular patterns (PAMPs) and self-derived molecules derived from damaged cells, referred as damage-associated molecules patterns (DAMPs). PRRs activate downstream signalling pathways that lead to the induction of innate immune responses by producing inflammatory cytokines, type I interferon (IFN), and other mediators. These processes not only trigger immediate host defensive responses such as inflammation, but also prime and orchestrate antigen-specific adaptive immune responses. These responses are essential for the clearance of infecting microbes as well as crucial for the consequent instruction of antigen-specific adaptive immune responses.
The discovery of TLRs and their cell biology provides new opportunities for drug intervention to manipulate immune responses. TLRs are most clearly associated with initiation of the innate response and inflammation and inhibition of TLR activity may help combat an overactive innate response characteristic of numerous inflammatory disorders.Vaccines for diseases such as AIDS, hepatitis C, malaria, and even cancer might be made more effective by supplementing them with TLR activators that stimulate dendritic cells. The activated dendritic cells then produce a more effective adaptive immune response. For example, scientists have linked a conserved component of influenza viruses with an agonist sato TLR5 to create a vaccine that could potentially protect against all strains of flu.