Pattern recognition receptors as potential drug targets in inflammatory disorders

Abstract

Pattern recognition receptors (PRRs) are a key part of the innate immune system, the body's first line of defense against infection and tissue damage. This superfamily of receptors including Toll-like receptors (TLRs), NOD-like receptors (NLRs), C-type lectin-like receptors (CLRs) and RIG-like receptors (RLRs) are responsible for initiation of the inflammatory response by their recognition of molecular patterns present in invading microorganisms (such as bacteria, viruses or fungi) during infection or in molecules released following tissue damage during acute or chronic disease states (such as sepsis or arthritis). These receptors are widely expressed and located on the cell surface, in intracellular compartments or in the cytoplasm can detect a single or subset of molecules including lipoproteins, carbohydrates or nucleic acids. In response, they initiate an intracellular signaling cascade that culminates in the synthesis and release of cytokines, chemokines and vasoactive molecules. These steps are necessary to maintain tissue homeostasis and remove potentially dangerous pathogens. However, during extreme or acute responses or during chronic disease, this can be damaging and even lead to death. Therefore, it is thought that targeting such receptors may offer a therapeutic approach in chronic inflammatory diseases or in cases of acute infection leading to sepsis. Herein, the current knowledge on the molecular biology of PRRs is reviewed along with their association with inflammatory and infectious diseases. Finally, the testing of therapeutic compounds and their future merit as targets is discussed.

Keywords: Anti-inflammatory drugs; C-type lectin-like receptors; Infection; Inflammatory disease; NOD-like receptors; Pattern recognition receptors; RIG-like receptors; Toll-like receptors.