Toll-like receptor 6

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Toll-like receptor 6 (TLR6) is a protein that in humans is encoded by the TLR6 gene. TLR6 is one of the Toll-like receptors, a type of protein that plays a critical role in the immune system, recognizing pathogens and activating immune responses. It is a member of the Toll-like receptor family, which is essential for pathogen recognition and innate immunity.

Function

TLR6, in partnership with TLR2, recognizes diacylated lipopeptides and lipoteichoic acids from Gram-positive bacteria, as well as zymosan from fungi. This recognition contributes to the activation of the NF-κB signaling pathway, leading to the production of necessary cytokines for the immune response. Unlike TLR4, which recognizes lipopolysaccharides from Gram-negative bacteria, TLR6 and TLR2 together have a unique specificity towards microbial components from Gram-positive bacteria and fungi.

Structure

The structure of TLR6, similar to other Toll-like receptors, includes an extracellular domain containing leucine-rich repeats (LRRs) and a cytoplasmic Toll/IL-1 receptor (TIR) domain. The LRRs are involved in ligand recognition, while the TIR domain is crucial for initiating downstream signaling pathways.

Signaling Pathway

Upon ligand binding, TLR6 dimerizes with TLR2, leading to the recruitment of adaptor proteins such as MyD88 and TIRAP/MAL. This recruitment initiates a signaling cascade that results in the activation of NF-κB and the production of pro-inflammatory cytokines. This process is vital for the initiation of the immune response against pathogens.

Clinical Significance

Alterations in TLR6 function can influence susceptibility to infections and the development of certain diseases. Variations in the TLR6 gene have been associated with differences in the risk of developing conditions such as asthma, allergic rhinitis, and other inflammatory diseases. Understanding the role of TLR6 in disease can help in the development of new therapeutic strategies targeting the innate immune response.

Research

Research on TLR6 continues to uncover its roles beyond pathogen recognition. Studies have suggested its involvement in the recognition of endogenous ligands and the development of autoimmunity. Furthermore, TLR6, along with other Toll-like receptors, is being explored as a target for novel vaccines and immunotherapies.

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Contributors: Prab R. Tumpati, MD