Disease relevance of TLR6

• TLR1 and TLR6 may participate in the activation of macrophages by Gram-positive bacteria, whereas TLR9 appears to respond to a specific sequence of bacterial DNA [1].
• There was a negative association between TLR6 S249P and ulcerative colitis with proctitis only (P = .026, OR [95% CI] 0.223 [0.096-0.705]) [2].
• In this study, we investigated whether sequence variants in the TLR6-TLR1-TLR10 gene cluster, residing within a 54-kb region on 4p14, were associated with prostate cancer risk [3].
• Using cells from knockout mice and genetic complementation in epithelial cells we found that highly pure LTA from both GBS and Staphylococcus aureus interact with TLR2 and TLR6, but not TLR1, in contrast to previous reports [4].
• Porcine TLR2 and TLR6: identification and their involvement in Mycoplasma hyopneumoniae infection [5].

High impact information on TLR6

• Finally, we show that TLR6, TLR2, and TLR1 are recruited to macrophage phagosomes that contain IgG-coated erythrocytes that do not display microbial components [6].
• TLR6 and TLR2 both are recruited to the macrophage phagosome, where they recognize peptidoglycan, a Gram-positive pathogen component [6].
• In addition, unlike TLR1 and TLR6, TLR10 was expressed in a highly restricted fashion as a highly N-glycosylated protein, which we detected in B cell lines, B cells from peripheral blood, and plasmacytoid dendritic cells from tonsil [7].
• Confocal microscopic analysis revealed that TLR6 was colocalized with TLR2 at the plasma membrane of monocytes [8].
• However, response to protein I/II stimulation was independent of TLR4, TLR2, and TLR6 [9].
• TLR6 has sense Alu elements in its 3'UTR region, making it susceptible to the regulation of other protein-coding or non-coding RNAs with antisense Alu elements [10].

Biological context of TLR6

• The TLR6 gene, as well as the TLR1 gene, mapped to the proximal region of murine chromosome 5 within 1.7cM of each other [11].
• The amino acid sequence of human TLR6 (hTLR6) is most similar to that of hTLR1 with 69% identity [11].
• We report here that two members of the TLR family, TLR2 and TLR6, together coordinate macrophage activation by Gram-positive bacteria and the yeast cell-wall particle, zymosan [6].
• We resequenced TLR6 in DNA samples from 24 African Americans, 23 European Americans, and 24 Hispanic Americans, identifying 53 SNPs, 22 with an allele frequency >5% [12].
• The open reading frames (ORFs) of the porcine TLR2 and TLR6 cDNA were shown to be 2358 and 2391 bp in length and to encode 785 and 796 amino acids, respectively [5].

Anatomical context of TLR6

• TLR2, TLR6 and TLR4 were expressed in human placental trophoblast cells [13].
• We reported previously that a secreted GBS "factor" activates phagocytes via Toll-like receptor (TLR)2 and TLR6, but that GBS cell walls activate cells independently of these receptors [14].
• Human colonic epithelial cells isolated by laser capture microscopy and IEC lines (Caco-2, T84, HT-29) were analyzed for expression of TLR2, TLR6, TLR1, and Toll inhibitory protein (Tollip) mRNA by RT-PCR and quantitative real-time PCR [15].
• Human TLR2 is expressed on the cell surface in a variety of cells, including monocytes, neutrophils, and monocyte-derived, immature dendritic cells (iDCs), whereas the expression profile of TLR6 in human cells remains obscure [8].
• In this study we produced a function-blocking mAb against human TLR6 and analyzed TLR6 expression in human blood cells and cell lines and its participation in ligand recognition [8].

Associations of TLR6 with chemical compounds

• Cutting edge: functional interactions between toll-like receptor (TLR) 2 and TLR1 or TLR6 in response to phenol-soluble modulin [16].
• However, neither lauric acid nor DHA affected the heterodimerization of TLR2 with TLR6 as well as the homodimerization of TLR4 as determined by co-immunoprecipitation assays in 293T cells in which these TLRs were transiently overexpressed [17].
• We successfully cloned and sequenced porcine toll-like receptor (TLR2) and TLR6 cDNA from porcine alveolar macrophages stimulated with 10 microg/ml lipopolysaccharide (LPS) [5].

Other interactions of TLR6

• TLR1 and TLR6 were expressed in all cell types examined [18].
• TLR6 associates with TLR2 and recognizes diacylated mycoplasmal lipopeptide along with TLR2 [19].
• Here we show that TLR6-deficient (TLR6(-/-)) cells are unresponsive to MALP-2 but retain their normal responses to lipopeptides of other bacterial origins [20].
• Compared with wild-type cells, which produced large amounts of TNF-alpha after incubation with PLM, the deletion of the TLR4 and TLR6 genes led to a limited alteration of the PLM-induced response [21].

Analytical, diagnostic and therapeutic context of TLR6

• We report here the molecular cloning and characterization of a new member of Toll-like receptor family, Toll-like receptor 6 (TLR6) [11].
• Western blot analysis confirmed that TLR2 and TLR6 proteins were both expressed in porcine alveolar macrophages [5].
• RESULTS: Reverse transcription-polymerase chain reaction (RT-PCR) demonstrated that TLR1 and TLR6 mRNA were expressed in platelets and Meg-01 cells [22].
• Flow cytometry analysis revealed the expression of TLR1 and TLR6 on the cell surface of Meg-01 cells [22].
• TLR1 and TLR6 Polymorphisms Are Associated with Susceptibility to Invasive Aspergillosis after Allogeneic Stem Cell Transplantation [23].

References