Abstract

THE ROLE OF TOLL LIKE RECEPTORS IN INNATE IMMUNITY

Dr. Lakshmi R.* and Dr. K. K. Jayavardhanan

Abstract

Toll-like receptors (TLRs) are the best-characterized membrane-bound receptors in innate immune cells, including macrophages and dendritic cells. 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 cellwall components such as lipopolysaccharides, peptidoglycans and lipopeptides, as well as flagellin, bacterial DNA and viral doublestranded 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 proinflammatory 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. Thirteen TLRs (named simply TLR1 to TLR13) have been identified in humans and mice together, and equivalent forms of many of these have been found in other mammalian species. 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.

Keywords: TLRs, PAMPs, lipopeptides, flagellin, bacterial DNA, viral double-stranded RNA.