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Gene Review

TLR1  -  toll-like receptor 1

Homo sapiens

Synonyms: CD281, KIAA0012, TIL, Toll-like receptor 1, Toll/interleukin-1 receptor-like protein, ...
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Disease relevance of TLR1


Psychiatry related information on TLR1


High impact information on TLR1

  • Other mutations, induced by the random germ line mutagen ENU (N-ethyl-N-nitrosourea), have disclosed key molecules in the TLR signaling pathways and helped us to construct a reasonably sophisticated portrait of the afferent innate immune response [8].
  • GENETIC ANALYSIS OF HOST RESISTANCE: Toll-Like Receptor Signaling and Immunity at Large [8].
  • IPCs display plasma cell morphology, selectively express Toll-like receptor (TLR)-7 and TLR9, and are specialized in rapidly secreting massive amounts of type 1 interferon following viral stimulation [9].
  • PTX3 is produced by a variety of cells and tissues, most notably dendritic cells and macrophages, in response to Toll-like receptor (TLR) engagement and inflammatory cytokines [10].
  • Upon recognition of microbial products, Toll-like receptors (TLRs) recruit distinct combinations of adaptors to induce TLR-specific gene expression [11].

Chemical compound and disease context of TLR1


Biological context of TLR1


Anatomical context of TLR1

  • TLR1 and TLR3 were only detectable in blood monocytes [21].
  • Neutrophils expressed TLR1, 2, 4, 5, 6, 7, 8, 9, and 10-all the TLRs except TLR3 [22].
  • An in vitro study in THP1 cells suggested that this relative increase in hsTLR1 might be attributable to a direct effect of mycobacterial components because it could be mimicked by mycobacterial preparations in the absence of IFN-gamma or T cells and by the TLR1/2 agonist Pam3CysK4 [23].
  • 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 [24].
  • Macrophages from TLR1-deficient (TLR1(-/-)) mice showed impaired proinflammatory cytokine production in response to the 19-kDa lipoprotein and a synthetic triacylated lipopeptide [17].

Associations of TLR1 with chemical compounds

  • Examination of chimeric receptors, generated by domain exchange between TLR1 and -6, has revealed that leucine-rich repeats 9-12 of the extracellular domain enable these receptors to discriminate between structurally similar lipopeptides [25].
  • However, examination of a wide variety of lipopeptide derivatives indicates that recognition by human TLR1 and -2 does not strictly correlate with the number or position of the acyl chains on the modified cysteine residue [25].
  • Cutting edge: functional interactions between toll-like receptor (TLR) 2 and TLR1 or TLR6 in response to phenol-soluble modulin [26].
  • Monocyte TLRs were upregulated in vivo (TLR1 and 2), and in vitro (TLR1, 2 and 4) 8 h after LPS bolus (P < 0.05 versus baseline) [27].
  • Inhibition of neutrophil apoptosis by TLR agonists in whole blood: involvement of the phosphoinositide 3-kinase/Akt and NF-kappaB signaling pathways, leading to increased levels of Mcl-1, A1, and phosphorylated Bad [28].

Physical interactions of TLR1

  • Taken together, TLR1 interacts with TLR2 to recognize the lipid configuration of the native mycobacterial lipoprotein as well as several triacylated lipopeptides [17].
  • In order to mediate cellular response to lipopolysaccharide (LPS), Toll-like receptor (TLR) 4 must interact with MD-2, a secreted protein [29].
  • TLR-ligand binding results in cell signal transduction and subsequent production of various proinflammatory cytokines such as IL-1 and TNF-alpha [30].
  • The activity of the secreted material was significantly reduced by anti-CD14 monoclonal antibodies suggesting that the active protein (or proteins) was binding to the CD14/Toll-like receptor (TLR)4 complex [31].
  • BACKGROUND: This study aimed to investigate the interrelationship of in vivo expression of lipopolysaccharide-binding protein (LBP) and membrane-bound CD14 (mCD14) in human gingival tissues as well as the coexpression of Toll-like receptors (TLR) 2 and 4 in association with periodontal conditions [32].

Regulatory relationships of TLR1


Other interactions of TLR1

  • TLR1 and TLR4 expression were not significantly induced by B-cell activation [37].
  • The lack of sensitization to TLR2 ligands by P. acnes correlated with no increase in hepatic TLR1 or TLR6 mRNA [38].
  • An increased level of hsTLR1 mRNA was found in both CD3- (p = 0.0078) and CD4+ cells (p = 0.028), resulting in an increased ratio of hsTLR1 mRNA to TLR1 and to TLR6 mRNA [23].
  • In addition, selective regulation of TLR7 expression in PDC and B cells by CpG ODN revealed TLR7 as a candidate TLR potentially involved in modulating the recognition of CpG motifs [39].
  • These results demonstrate that TLR1 through TLR5 mRNAs are differentially expressed and regulated in human leukocytes [33].

Analytical, diagnostic and therapeutic context of TLR1


  1. Hyporesponsiveness to vaccination with Borrelia burgdorferi OspA in humans and in TLR1- and TLR2-deficient mice. Alexopoulou, L., Thomas, V., Schnare, M., Lobet, Y., Anguita, J., Schoen, R.T., Medzhitov, R., Fikrig, E., Flavell, R.A. Nat. Med. (2002) [Pubmed]
  2. Peptidoglycan- and lipoteichoic acid-induced cell activation is mediated by toll-like receptor 2. Schwandner, R., Dziarski, R., Wesche, H., Rothe, M., Kirschning, C.J. J. Biol. Chem. (1999) [Pubmed]
  3. Borrelia burgdorferi lipoprotein-mediated TLR2 stimulation causes the down-regulation of TLR5 in human monocytes. Cabral, E.S., Gelderblom, H., Hornung, R.L., Munson, P.J., Martin, R., Marques, A.R. J. Infect. Dis. (2006) [Pubmed]
  4. Toll-like receptor-1, -2, and -6 polymorphisms influence disease extension in inflammatory bowel diseases. Pierik, M., Joossens, S., Van Steen, K., Van Schuerbeek, N., Vlietinck, R., Rutgeerts, P., Vermeire, S. Inflamm. Bowel Dis. (2006) [Pubmed]
  5. Immune cell activation by bacterial CpG-DNA through myeloid differentiation marker 88 and tumor necrosis factor receptor-associated factor (TRAF)6. Häcker, H., Vabulas, R.M., Takeuchi, O., Hoshino, K., Akira, S., Wagner, H. J. Exp. Med. (2000) [Pubmed]
  6. Role of toll-like receptor signalling in Abeta uptake and clearance. Tahara, K., Kim, H.D., Jin, J.J., Maxwell, J.A., Li, L., Fukuchi, K. Brain (2006) [Pubmed]
  7. Rheumatoid factor induction in murine models of liver injury. Nowak, U., Gill, K., Skamene, E., Newkirk, M.M. Clin. Exp. Immunol. (2007) [Pubmed]
  8. GENETIC ANALYSIS OF HOST RESISTANCE: Toll-Like Receptor Signaling and Immunity at Large. Beutler, B., Jiang, Z., Georgel, P., Crozat, K., Croker, B., Rutschmann, S., Du, X., Hoebe, K. Annu. Rev. Immunol. (2006) [Pubmed]
  9. IPC: professional type 1 interferon-producing cells and plasmacytoid dendritic cell precursors. Liu, Y.J. Annu. Rev. Immunol. (2005) [Pubmed]
  10. Pentraxins at the crossroads between innate immunity, inflammation, matrix deposition, and female fertility. Garlanda, C., Bottazzi, B., Bastone, A., Mantovani, A. Annu. Rev. Immunol. (2005) [Pubmed]
  11. Sorting out Toll signals. Fitzgerald, K.A., Chen, Z.J. Cell (2006) [Pubmed]
  12. Human Langerhans Cells Express a Specific TLR Profile and Differentially Respond to Viruses and Gram-Positive Bacteria. Flacher, V., Bouschbacher, M., Verron??se, E., Massacrier, C., Sisirak, V., Berthier-Vergnes, O., de Saint-Vis, B., Caux, C., Dezutter-Dambuyant, C., Lebecque, S., Valladeau, J. J. Immunol. (2006) [Pubmed]
  13. Modulation of expression and function of Toll-like receptor 3 in A549 and H292 cells by histamine. Hou, Y.F., Zhou, Y.C., Zheng, X.X., Wang, H.Y., Fu, Y.L., Fang, Z.M., He, S.H. Mol. Immunol. (2006) [Pubmed]
  14. Liposomal amphotericin B activates antifungal resistance with reduced toxicity by diverting Toll-like receptor signalling from TLR-2 to TLR-4. Bellocchio, S., Gaziano, R., Bozza, S., Rossi, G., Montagnoli, C., Perruccio, K., Calvitti, M., Pitzurra, L., Romani, L. J. Antimicrob. Chemother. (2005) [Pubmed]
  15. Human toll-like receptors mediate cellular activation by Mycobacterium tuberculosis. Means, T.K., Wang, S., Lien, E., Yoshimura, A., Golenbock, D.T., Fenton, M.J. J. Immunol. (1999) [Pubmed]
  16. Evidence for an accessory protein function for Toll-like receptor 1 in anti-bacterial responses. Wyllie, D.H., Kiss-Toth, E., Visintin, A., Smith, S.C., Boussouf, S., Segal, D.M., Duff, G.W., Dower, S.K. J. Immunol. (2000) [Pubmed]
  17. Cutting edge: role of Toll-like receptor 1 in mediating immune response to microbial lipoproteins. Takeuchi, O., Sato, S., Horiuchi, T., Hoshino, K., Takeda, K., Dong, Z., Modlin, R.L., Akira, S. J. Immunol. (2002) [Pubmed]
  18. TLR6: A novel member of an expanding toll-like receptor family. Takeuchi, O., Kawai, T., Sanjo, H., Copeland, N.G., Gilbert, D.J., Jenkins, N.A., Takeda, K., Akira, S. Gene (1999) [Pubmed]
  19. Expression of toll-like receptors on B lymphocytes. Dasari, P., Nicholson, I.C., Hodge, G., Dandie, G.W., Zola, H. Cell. Immunol. (2005) [Pubmed]
  20. Sequence variants in Toll-like receptor gene cluster (TLR6-TLR1-TLR10) and prostate cancer risk. Sun, J., Wiklund, F., Zheng, S.L., Chang, B., Bälter, K., Li, L., Johansson, J.E., Li, G., Adami, H.O., Liu, W., Tolin, A., Turner, A.R., Meyers, D.A., Isaacs, W.B., Xu, J., Grönberg, H. J. Natl. Cancer Inst. (2005) [Pubmed]
  21. Toll-like receptors 2 and 4 are up-regulated during intestinal inflammation. Hausmann, M., Kiessling, S., Mestermann, S., Webb, G., Spöttl, T., Andus, T., Schölmerich, J., Herfarth, H., Ray, K., Falk, W., Rogler, G. Gastroenterology (2002) [Pubmed]
  22. Toll-like receptors stimulate human neutrophil function. Hayashi, F., Means, T.K., Luster, A.D. Blood (2003) [Pubmed]
  23. Myobacterium tuberculosis induces selective up-regulation of TLRs in the mononuclear leukocytes of patients with active pulmonary tuberculosis. Chang, J.S., Huggett, J.F., Dheda, K., Kim, L.U., Zumla, A., Rook, G.A. J. Immunol. (2006) [Pubmed]
  24. Human TLR10 is a functional receptor, expressed by B cells and plasmacytoid dendritic cells, which activates gene transcription through MyD88. Hasan, U., Chaffois, C., Gaillard, C., Saulnier, V., Merck, E., Tancredi, S., Guiet, C., Brière, F., Vlach, J., Lebecque, S., Trinchieri, G., Bates, E.E. J. Immunol. (2005) [Pubmed]
  25. Domain exchange between human toll-like receptors 1 and 6 reveals a region required for lipopeptide discrimination. Omueti, K.O., Beyer, J.M., Johnson, C.M., Lyle, E.A., Tapping, R.I. J. Biol. Chem. (2005) [Pubmed]
  26. Cutting edge: functional interactions between toll-like receptor (TLR) 2 and TLR1 or TLR6 in response to phenol-soluble modulin. Hajjar, A.M., O'Mahony, D.S., Ozinsky, A., Underhill, D.M., Aderem, A., Klebanoff, S.J., Wilson, C.B. J. Immunol. (2001) [Pubmed]
  27. Endotoxaemia modulates Toll-like receptors on leucocytes in humans. Marsik, C., Mayr, F., Cardona, F., Derhaschnig, U., Wagner, O.F., Jilma, B. Br. J. Haematol. (2003) [Pubmed]
  28. Inhibition of neutrophil apoptosis by TLR agonists in whole blood: involvement of the phosphoinositide 3-kinase/Akt and NF-kappaB signaling pathways, leading to increased levels of Mcl-1, A1, and phosphorylated Bad. François, S., El Benna, J., Dang, P.M., Pedruzzi, E., Gougerot-Pocidalo, M.A., Elbim, C. J. Immunol. (2005) [Pubmed]
  29. Monomeric recombinant MD-2 binds toll-like receptor 4 tightly and confers lipopolysaccharide responsiveness. Re, F., Strominger, J.L. J. Biol. Chem. (2002) [Pubmed]
  30. Toll-like receptors 2, 3 and 4 (TLR-2, TLR-3 and TLR-4) are expressed in the microenvironment of human acquired cholesteatoma. Szczepański, M., Szyfter, W., Jenek, R., Wróbel, M., Lisewska, I.M., Zeromski, J. European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery. (2006) [Pubmed]
  31. Streptococcus sanguis secretes CD14-binding proteins that stimulate cytokine synthesis: a clue to the pathogenesis of infective (bacterial) endocarditis? Banks, J., Poole, S., Nair, S.P., Lewthwaite, J., Tabona, P., McNab, R., Wilson, M., Paul, A., Henderson, B. Microb. Pathog. (2002) [Pubmed]
  32. The expression profile of lipopolysaccharide-binding protein, membrane-bound CD14, and toll-like receptors 2 and 4 in chronic periodontitis. Ren, L., Leung, W.K., Darveau, R.P., Jin, L. J. Periodontol. (2005) [Pubmed]
  33. Differential expression and regulation of toll-like receptors (TLR) in human leukocytes: selective expression of TLR3 in dendritic cells. Muzio, M., Bosisio, D., Polentarutti, N., D'amico, G., Stoppacciaro, A., Mancinelli, R., van't Veer, C., Penton-Rol, G., Ruco, L.P., Allavena, P., Mantovani, A. J. Immunol. (2000) [Pubmed]
  34. Toll-like receptor 1 inhibits Toll-like receptor 4 signaling in endothelial cells. Spitzer, J.H., Visintin, A., Mazzoni, A., Kennedy, M.N., Segal, D.M. Eur. J. Immunol. (2002) [Pubmed]
  35. TIR-containing adapter molecule (TICAM)-2, a bridging adapter recruiting to toll-like receptor 4 TICAM-1 that induces interferon-beta. Oshiumi, H., Sasai, M., Shida, K., Fujita, T., Matsumoto, M., Seya, T. J. Biol. Chem. (2003) [Pubmed]
  36. Regulation of PTX3, a key component of humoral innate immunity in human dendritic cells: stimulation by IL-10 and inhibition by IFN-gamma. Doni, A., Michela, M., Bottazzi, B., Peri, G., Valentino, S., Polentarutti, N., Garlanda, C., Mantovani, A. J. Leukoc. Biol. (2006) [Pubmed]
  37. The toll-like receptor repertoire of human B lymphocytes: inducible and selective expression of TLR9 and TLR10 in normal and transformed cells. Bourke, E., Bosisio, D., Golay, J., Polentarutti, N., Mantovani, A. Blood (2003) [Pubmed]
  38. Selective priming to Toll-like receptor 4 (TLR4), not TLR2, ligands by P. acnes involves up-regulation of MD-2 in mice. Romics, L., Dolganiuc, A., Kodys, K., Drechsler, Y., Oak, S., Velayudham, A., Mandrekar, P., Szabo, G. Hepatology (2004) [Pubmed]
  39. Quantitative expression of toll-like receptor 1-10 mRNA in cellular subsets of human peripheral blood mononuclear cells and sensitivity to CpG oligodeoxynucleotides. Hornung, V., Rothenfusser, S., Britsch, S., Krug, A., Jahrsdörfer, B., Giese, T., Endres, S., Hartmann, G. J. Immunol. (2002) [Pubmed]
  40. Human intestinal epithelial cells are broadly unresponsive to Toll-like receptor 2-dependent bacterial ligands: implications for host-microbial interactions in the gut. Melmed, G., Thomas, L.S., Lee, N., Tesfay, S.Y., Lukasek, K., Michelsen, K.S., Zhou, Y., Hu, B., Arditi, M., Abreu, M.T. J. Immunol. (2003) [Pubmed]
  41. Expression and regulation of Toll-like receptor 2 by IL-1beta and fibronectin fragments in human articular chondrocytes. Su, S.L., Tsai, C.D., Lee, C.H., Salter, D.M., Lee, H.S. Osteoarthr. Cartil. (2005) [Pubmed]
  42. Interferon regulatory factor 3 is involved in Toll-like receptor 4 (TLR4)- and TLR3-induced IL-12p35 gene activation. Goriely, S., Molle, C., Nguyen, M., Albarani, V., Haddou, N.O., Lin, R., De Wit, D., Flamand, V., Willems, F., Goldman, M. Blood (2006) [Pubmed]
  43. Toll-like receptor 2, 3, and 4 expression and function in human airway smooth muscle. Sukkar, M.B., Xie, S., Khorasani, N.M., Kon, O.M., Stanbridge, R., Issa, R., Chung, K.F. J. Allergy Clin. Immunol. (2006) [Pubmed]
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