Therapeutic boosting of the immune response: turning to CD14 for help

The Toll-like family of immune receptors (TLRs) are critical for an efficient immune response to a variety of microorganisms and other antigens that may cause pathology. Modulating immune responses by targeting TLRs therefore has substantial therapeutic potential, and a number of TLR-based therapeutic strategies have been developed. Minimizing the adverse effects that may result from the therapeutic manipulation of these signalling receptors nevertheless remains a major challenge. Efficient responses via TLRs require the activity of the co-receptor CD14, which enhances TLR responses. In an attempt to boost the immune response for therapeutic purposes, we have sought to target CD14 to achieve TLR modulation. Here we discuss the design, activity and therapeutic development options of TLR-derived peptides that interact with CD14 and enhance its co-receptor activity, thus amplifying TLR-mediated responses. This strategy represents a promising alternative to current TLR-based therapies, as it has the potential to amplify responses to different pathogens mediated by different TLRs by targeting the common TLR co-receptor, CD14.