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Gene Review

Tlr9  -  toll-like receptor 9

Mus musculus

Synonyms: Toll-like receptor 9
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Disease relevance of Tlr9

  • Compared with wild-type animals, T. cruzi-infected Tlr9(-/-) mice displayed elevated parasitemia and decreased survival [1].
  • PDC activation of CD3(+)T cells in response to EBV stimulation was dependent on cell-to-cell contact, in part mediated by toll-like receptor 9 (TLR-9) signaling that was inhibited by chloroquine and TLR-9 inhibitory CpG [2].
  • Role of Toll-Like Receptor 9 in Legionella pneumophila-Induced Interleukin-12 p40 Production in Bone Marrow-Derived Dendritic Cells and Macrophages from Permissive and Nonpermissive Mice [3].
  • Toll-like receptor 9 controls anti-DNA autoantibody production in murine lupus [4].
  • These results indicate that TLR9-triggered type I IFN has antiinflammatory functions in colitis [5].

High impact information on Tlr9


Biological context of Tlr9

  • Here, we describe a codominant CpG-ODN unresponsive phenotype that results from an N-ethyl-N-nitrosourea-induced missense mutation in the Tlr9 gene (Tlr9(CpG1)) [10].
  • Such potent adjuvant activities of CpG-liposome were absent in TLR9-deficient mice, indicating that CpG-liposome was as effective as CpG-ODN in stimulating type 1 innate immunity through TLR9 [11].
  • CpG oligodeoxynucleotides (ODN) activate immune cells to produce immune mediators by Toll-like receptor 9 (TLR9)-mediated signal transduction, which activates mitogen-activated protein kinases (MAPKs) and nuclear factor-kappaB (NF-kappaB) through the MyD88/IRAK/TRAF6 kinases cascade [12].
  • RT-PCR experiments revealed that CpG-N ODN treatment could down-regulate the CpG-S ODN-induced upregulation of Toll-like receptor 9 (TLR9) mRNA expression [13].
  • In this study, we demonstrate for the first time that murine TLR9 binds an unmethylated CpG-containing plasmid [14].

Anatomical context of Tlr9


Associations of Tlr9 with chemical compounds


Regulatory relationships of Tlr9


Other interactions of Tlr9


Analytical, diagnostic and therapeutic context of Tlr9


  1. Cutting Edge: TLR9 and TLR2 Signaling Together Account for MyD88-Dependent Control of Parasitemia in Trypanosoma cruzi Infection. Bafica, A., Santiago, H.C., Goldszmid, R., Ropert, C., Gazzinelli, R.T., Sher, A. J. Immunol. (2006) [Pubmed]
  2. Human plasmacytoid dendritic cells regulate immune responses to Epstein-Barr virus (EBV) infection and delay EBV-related mortality in humanized NOD-SCID mice. Lim, W.H., Kireta, S., Russ, G.R., Coates, P.T. Blood (2007) [Pubmed]
  3. Role of Toll-Like Receptor 9 in Legionella pneumophila-Induced Interleukin-12 p40 Production in Bone Marrow-Derived Dendritic Cells and Macrophages from Permissive and Nonpermissive Mice. Newton, C.A., Perkins, I., Widen, R.H., Friedman, H., Klein, T.W. Infect. Immun. (2007) [Pubmed]
  4. Toll-like receptor 9 controls anti-DNA autoantibody production in murine lupus. Christensen, S.R., Kashgarian, M., Alexopoulou, L., Flavell, R.A., Akira, S., Shlomchik, M.J. J. Exp. Med. (2005) [Pubmed]
  5. Toll-like receptor 9-induced type I IFN protects mice from experimental colitis. Katakura, K., Lee, J., Rachmilewitz, D., Li, G., Eckmann, L., Raz, E. J. Clin. Invest. (2005) [Pubmed]
  6. Lymphoid follicle destruction and immunosuppression after repeated CpG oligodeoxynucleotide administration. Heikenwalder, M., Polymenidou, M., Junt, T., Sigurdson, C., Wagner, H., Akira, S., Zinkernagel, R., Aguzzi, A. Nat. Med. (2004) [Pubmed]
  7. Activation of autoreactive B cells by CpG dsDNA. Viglianti, G.A., Lau, C.M., Hanley, T.M., Miko, B.A., Shlomchik, M.J., Marshak-Rothstein, A. Immunity (2003) [Pubmed]
  8. Interaction between conventional dendritic cells and natural killer cells is integral to the activation of effective antiviral immunity. Andoniou, C.E., van Dommelen, S.L., Voigt, V., Andrews, D.M., Brizard, G., Asselin-Paturel, C., Delale, T., Stacey, K.J., Trinchieri, G., Degli-Esposti, M.A. Nat. Immunol. (2005) [Pubmed]
  9. TLR9 signals after translocating from the ER to CpG DNA in the lysosome. Latz, E., Schoenemeyer, A., Visintin, A., Fitzgerald, K.A., Monks, B.G., Knetter, C.F., Lien, E., Nilsen, N.J., Espevik, T., Golenbock, D.T. Nat. Immunol. (2004) [Pubmed]
  10. Toll-like receptors 9 and 3 as essential components of innate immune defense against mouse cytomegalovirus infection. Tabeta, K., Georgel, P., Janssen, E., Du, X., Hoebe, K., Crozat, K., Mudd, S., Shamel, L., Sovath, S., Goode, J., Alexopoulou, L., Flavell, R.A., Beutler, B. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  11. Liposome-encapsulated CpG oligodeoxynucleotides as a potent adjuvant for inducing type 1 innate immunity. Suzuki, Y., Wakita, D., Chamoto, K., Narita, Y., Tsuji, T., Takeshima, T., Gyobu, H., Kawarada, Y., Kondo, S., Akira, S., Katoh, H., Ikeda, H., Nishimura, T. Cancer Res. (2004) [Pubmed]
  12. Ras participates in CpG oligodeoxynucleotide signaling through association with toll-like receptor 9 and promotion of interleukin-1 receptor-associated kinase/tumor necrosis factor receptor-associated factor 6 complex formation in macrophages. Xu, H., An, H., Yu, Y., Zhang, M., Qi, R., Cao, X. J. Biol. Chem. (2003) [Pubmed]
  13. The newly identified CpG-N ODN208 protects mice from challenge with CpG-S ODN by decreasing TNF-alpha release. Wang, L., Jiang, W., Ding, G., Cao, H., Lu, Y., Luo, P., Zhou, H., Zheng, J. Int. Immunopharmacol. (2007) [Pubmed]
  14. Direct evidence that toll-like receptor 9 (TLR9) functionally binds plasmid DNA by specific cytosine-phosphate-guanine motif recognition. Cornélie, S., Hoebeke, J., Schacht, A.M., Bertin, B., Vicogne, J., Capron, M., Riveau, G. J. Biol. Chem. (2004) [Pubmed]
  15. The roles of Toll-like receptor 9, MyD88, and DNA-dependent protein kinase catalytic subunit in the effects of two distinct CpG DNAs on dendritic cell subsets. Hemmi, H., Kaisho, T., Takeda, K., Akira, S. J. Immunol. (2003) [Pubmed]
  16. CpG oligodeoxynucleotides induce expression of proinflammatory cytokines and chemokines in astrocytes: the role of c-Jun N-terminal kinase in CpG ODN-mediated NF-kappaB activation. Lee, S., Hong, J., Choi, S.Y., Oh, S.B., Park, K., Kim, J.S., Karin, M., Lee, S.J. J. Neuroimmunol. (2004) [Pubmed]
  17. Synergistic action of immunostimulatory DNA and fcgamma receptor IIB-crosslinking on B-cell phenotype and function. Bjersing, J.L., Tarkowski, A., Lundin, S., Collins, L.V. Immunobiology (2005) [Pubmed]
  18. Genetic analysis of the innate immune responses in wild-derived inbred strains of mice. Stephan, K., Smirnova, I., Jacque, B., Poltorak, A. Eur. J. Immunol. (2007) [Pubmed]
  19. Colony-stimulating factor-1 suppresses responses to CpG DNA and expression of toll-like receptor 9 but enhances responses to lipopolysaccharide in murine macrophages. Sweet, M.J., Campbell, C.C., Sester, D.P., Xu, D., McDonald, R.C., Stacey, K.J., Hume, D.A., Liew, F.Y. J. Immunol. (2002) [Pubmed]
  20. Myeloid differentiation factor 88-dependent post-transcriptional regulation of cyclooxygenase-2 expression by CpG DNA: tumor necrosis factor-alpha receptor-associated factor 6, a diverging point in the Toll-like receptor 9-signaling. Yeo, S.J., Yoon, J.G., Yi, A.K. J. Biol. Chem. (2003) [Pubmed]
  21. Involvement of the Toll-like receptor 9 signaling pathway in the induction of innate immunity by baculovirus. Abe, T., Hemmi, H., Miyamoto, H., Moriishi, K., Tamura, S., Takaku, H., Akira, S., Matsuura, Y. J. Virol. (2005) [Pubmed]
  22. Toll-like receptor 9 regulates tumor necrosis factor-alpha expression by different mechanisms. Implications for osteoclastogenesis. Amcheslavsky, A., Zou, W., Bar-Shavit, Z. J. Biol. Chem. (2004) [Pubmed]
  23. Amyloid beta peptide 1-40 enhances the action of Toll-like receptor-2 and -4 agonists but antagonizes Toll-like receptor-9-induced inflammation in primary mouse microglial cell cultures. Lotz, M., Ebert, S., Esselmann, H., Iliev, A.I., Prinz, M., Wiazewicz, N., Wiltfang, J., Gerber, J., Nau, R. J. Neurochem. (2005) [Pubmed]
  24. DNA-PKcs, but not TLR9, is required for activation of Akt by CpG-DNA. Dragoi, A.M., Fu, X., Ivanov, S., Zhang, P., Sheng, L., Wu, D., Li, G.C., Chu, W.M. EMBO J. (2005) [Pubmed]
  25. IRF-7 is the master regulator of type-I interferon-dependent immune responses. Honda, K., Yanai, H., Negishi, H., Asagiri, M., Sato, M., Mizutani, T., Shimada, N., Ohba, Y., Takaoka, A., Yoshida, N., Taniguchi, T. Nature (2005) [Pubmed]
  26. CpG directly induces T-bet expression and inhibits IgG1 and IgE switching in B cells. Liu, N., Ohnishi, N., Ni, L., Akira, S., Bacon, K.B. Nat. Immunol. (2003) [Pubmed]
  27. Murine liver plasmacytoid dendritic cells become potent immunostimulatory cells after Flt-3 ligand expansion. Kingham, T.P., Chaudhry, U.I., Plitas, G., Katz, S.C., Raab, J., DeMatteo, R.P. Hepatology (2007) [Pubmed]
  28. TLR9 pathway is involved in adjuvant effects of plasmid DNA-based vaccines. Tudor, D., Dubuquoy, C., Gaboriau, V., Lefèvre, F., Charley, B., Riffault, S. Vaccine (2005) [Pubmed]
  29. Degranulation of paneth cells via toll-like receptor 9. Rumio, C., Besusso, D., Palazzo, M., Selleri, S., Sfondrini, L., Dubini, F., Ménard, S., Balsari, A. Am. J. Pathol. (2004) [Pubmed]
  30. Differential contribution of osteoclast- and osteoblast-lineage cells to CpG-oligodeoxynucleotide (CpG-ODN) modulation of osteoclastogenesis. Amcheslavsky, A., Hemmi, H., Akira, S., Bar-Shavit, Z. J. Bone Miner. Res. (2005) [Pubmed]
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