Toll-like receptors and their role in innate immunity

The innate immune system is an ancient mechanism of host defence found in essentially every multicellular organism, from plants to humans. In invertebrates, it is the only mechanism of defence. Vertebrates also developed an adaptive immune response; however, the innate immune system is essential for instructing the cells of the adaptive system (T and B cells). Toll-like receptors (TLRs) play an important role in innate immunity to invading pathogens by sensing microorganisms. These evolutionary conserved receptors, homologues of the Drosophila Toll gene, recognize highly conserved structural motifs only expressed by microbial pathogens, called pathogen-associated microbial patterns (PAMPs). PAMPs include various bacterial cell-wall components such as lipopolysaccharides, peptidoglycans and lipopeptides, as well as flagellin, bacterial DNA and viral double-stranded RNA. Stimulation of TLRs by PAMPs initiates a signalling cascade that involves a number of proteins. This leads to the activation of the transcription factor NF-KB, which induces the secretion of pro-inflammatory cytokines and effector cytokines that direct the adaptive immune response. TLRs are predominantly expressed in tissues involved in immune function, such as spleen and peripheral blood leukocytes, as well as those exposed to the external environment such as lung and the gastrointestinal tract. Ten human and nine murine TLRs have been characterized and for many of them, ligands have been identified. In many cases, TLRs need the presence of co-receptors to initiate the signalling cascade, like CD14. Studies on TLRs indicate that these receptors are essential elements in host defence against pathogens by activating the innate immunity, a prerequisite to induction of adaptive immunity. The detailed study of TLRs will bring us closer to understanding the role of TLR-mediated responses and increase our range to treat infectious and immune diseases.