Therapeutic Boosting of the Immune Response: Turning to CD14 for Help

Abstract

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.

Fig. (1)

Schematic diagram illustrating the CD14-targeting strategy to boost TLR activity. TLR2-derived peptides increase CD14’s co-receptor activity, and thus enhance TLR responses, by specifically binding to CD14 and accelerating ligand transfer from CD14 to the TLR. This results in increased and sustained ligand occupancy of TLR, increased receptor clustering for signaling, and thus an amplified response.