Toll-like receptors: Potential targets for therapeutic interventions

Abstract

Members of the Toll-like receptor (TLR) family play critical roles as regulators of innate immune responses. TLRs have been described to bind to pathogen-associated molecular patterns (PAMPs) expressed on a broad variety of microbes including bacteria and viruses. Recognition of pathogenderived ligands by TLRs triggers the activation of nuclear factor κB (NF-κB) and type I interferon pathways that lead to the production of proinflammatory cytokines, an increase in natural killer cell cytotoxicity, and activation of T cells. In addition to the innate immune system, TLRs are also involved in shaping adaptive immune reactions. TLRs function as integral membrane glycoproteins that are characterized by extracellular domains containing variable numbers of leucine-rich repeat (LRR) motifs and a cytoplasmic Toll/interleukin (IL)-1 receptor (TIR) homology domain. In humans and mice, at least 12 TLRs have been identified which are engaged in different gene expression programs. Since TLRs act as key players in the pathogen-induced stimulation of dendritic cells, including antigen uptake and processing, as well as differentiation of CD4+ T cells, they may become interesting targets for future pharmacological interventions. In the following, we will briefly discuss the role of TLRs in the pathogenesis of inflammatory heart disease and particularly focus on their potential as targets for therapeutical interventions. © 2009 Springer Berlin Heidelberg.