TLR1 gene

The TLR1 gene (TLR1 stands for: Toll Like Receptor 1) is a protein-coding gene located on chromosome 4p14. Transcripts of different lengths have been detected for this gene, presumably due to the use of an alternative polyadenylation site and/or alternative splicing. An important paralog of this gene is TLR6.

The protein encoded by the TLR1 gene, Toll-Like Receptor 1, belongs to the Toll-like receptor (TLR) family, which plays a fundamental role in recognizing pathogens and activating innate immunity. TLRs are highly conserved from Drosophila to humans and show structural and functional similarities. They recognize pathogen-associated molecular patterns (PAMPs) expressed on infectious agents and mediate the production of cytokines necessary for the development of effective immunity. TLRs generally exist as homodimers (heterodimers have been reported) and are found on immune cells, macrophages, B lymphocytes and mast cells.

The different TLRs show different expression patterns, which is also reflected in the type of inflammatory infiltrates (e.g. the plasma cell is an indicative cell for spirochetosis).

The TLR1 protein receptor is involved in the innate immune response to microbial pathogens. Recognizes specifically diacylated and triacylated lipopeptides. It cooperates with the TLR2 receptor protein to mediate the innate immune response to bacterial lipoproteins or lipopeptides (Lancioni CL et al. 2011). The receptor protein TLR1 forms an activation cluster TLR2:TLR1:CD14 with TLR2 and CD14 in response to triacylated lipopeptides. This cluster triggers signaling from the cell surface and is subsequently transmitted to the Golgi apparatus via a lipid-raft-dependent pathway (Triantafilou M et al. 2006).

TLR1 acts via MYD88 and TRAF6 and leads to NF-kappaB activation, cytokine secretion and inflammatory response.

The TLR1 gene is ubiquitously expressed, and to a greater extent than other TLR genes. Diseases associated with TLR1 include leprosy, Lyme disease and rheumatoid arthritis.

1. Lancioni CL et al. (2011) Mycobacterium tuberculosis lipoproteins directly regulate human memory CD4(+) T cell activation via Toll-like receptors 1 and 2. Infect Immun 79:663-673.
2. Triantafilou M et al. (2006) Membrane sorting of toll-like receptor (TLR)-2/6 and TLR2/1 heterodimers at the cell surface determines heterotypic associations with CD36 and intracellular targeting. J Biol Chem 281:31002-31011.
3. Zhao H et al. (2019) Borrelia burgdorferi basic membrane protein A initiates proinflammatory chemokine storm in THP 1-derived macrophages via the receptors TLR1 and TLR2. Biomed Pharmacother 115:108874.