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TLR8

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Encyclopedia of Signaling Molecules

Synonyms

CD288; Toll-like receptor 8

Historical Background

Although sharing a similar structure, genomic localization, and involvement in RNA sensing, TLR7 and TLR8 are found in distinct immune cells (Hornung et al. 2002). This selective expression correlates with distinct biological functionality and production of type I IFNs (Gorden et al. 2005; Cervantes et al. 2011).

The initial observations that TLR8-deficient mice did not show any defect in nucleic acid detection, due to a lack of response to imidazoquinolines and RNA (Heil et al. 2004; Jurk et al. 2002), lead to a relative lack of interest in this particular endosomal TLR. Very recently it has been reported that overexpression of mTLR8 is required for the activation of transcription factor NF-κB and the production of TNF-α (Li et al. 2016). These results demonstrate that mTLR8 is indeed functional and does play a role in the activation of innate immune responses.

Structural Features of the TLR8 Ligand Recognition Domain

TLR8...

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References

  • Bergstrom B, Aune MH, Awuh JA, Kojen JF, Blix KJ, Ryan L, et al. TLR8 senses Staphylococcus aureus RNA in human primary monocytes and macrophages and induces IFN-beta production via a TAK1-IKKbeta-IRF5 signaling pathway. J Immunol. 2015;195(3):1100–11.

    Article  PubMed  CAS  Google Scholar 

  • Bruns H, Stenger S. New insights into the interaction of Mycobacterium tuberculosis and human macrophages. Future Microbiol. 2014;9(3):327–41.

    Article  PubMed  CAS  Google Scholar 

  • Bukhari M, Aslam MA, Khan A, Iram Q, Akbar A, Naz AG, et al. TLR8 gene polymorphism and association in bacterial load in southern Punjab of Pakistan: an association study with pulmonary tuberculosis. Int J Immunogenet. 2015;42(1):46–51.

    Article  PubMed  CAS  Google Scholar 

  • Cervantes JL, Dunham-Ems SM, La Vake CJ, Petzke MM, Sahay B, Sellati TJ, et al. Phagosomal signaling by Borrelia burgdorferi in human monocytes involves Toll-like receptor (TLR) 2 and TLR8 cooperativity and TLR8-mediated induction of IFN-beta. Proc Natl Acad Sci USA. 2011;108(9):3683–8.

    Article  PubMed  PubMed Central  Google Scholar 

  • Cervantes JL, Weinerman B, Basole C, Salazar JC. TLR8: the forgotten relative revindicated. Cell Mol Immunol. 2012;9(6):434–8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Cervantes JL, La Vake CJ, Weinerman B, Luu S, O’Connell C, Verardi PH, et al. Human TLR8 is activated upon recognition of Borrelia burgdorferi RNA in the phagosome of human monocytes. J Leukoc Biol. 2013;94(6):1231–41.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Chai HH, Lim D, Suk JE, Choi BH, Cho YM. Design of anti-BVDV drug based on common chemical features, their interaction, and scaffolds of TLR8 agonists. Int J Biol Macromol. 2016;92:1095–112.

    Article  PubMed  CAS  Google Scholar 

  • Conley ME. Immunodeficiency: UNC-93B gets a toll call. Trends Immunol. 2007;28(3):99–101.

    Article  PubMed  CAS  Google Scholar 

  • Dalgic N, Tekin D, Kayaalti Z, Cakir E, Soylemezoglu T, Sancar M. Relationship between toll-like receptor 8 gene polymorphisms and pediatric pulmonary tuberculosis. Dis Markers. 2011;31(1):33–8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Daud II, Scott ME, Ma Y, Shiboski S, Farhat S, Moscicki AB. Association between toll-like receptor expression and human papillomavirus type 16 persistence. Int J Cancer. 2011;128(4):879–86.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Davila S, Hibberd ML, Hari Dass R, Wong HE, Sahiratmadja E, Bonnard C, et al. Genetic association and expression studies indicate a role of toll-like receptor 8 in pulmonary tuberculosis. PLoS Genet. 2008;4(10):e1000218.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Demaria O, Pagni PP, Traub S, de Gassart A, Branzk N, Murphy AJ, et al. TLR8 deficiency leads to autoimmunity in mice. J Clin Invest. 2010;120(10):3651–62.

    PubMed  PubMed Central  CAS  Google Scholar 

  • Eigenbrod T, Pelka K, Latz E, Kreikemeyer B, Dalpke AH. TLR8 senses bacterial RNA in human monocytes and plays a nonredundant role for recognition of Streptococcus pyogenes. J Immunol. 2015;195(3):1092–9.

    Article  PubMed  CAS  Google Scholar 

  • Gantier MP, Irving AT, Kaparakis-Liaskos M, Xu D, Evans VA, Cameron PU, et al. Genetic modulation of TLR8 response following bacterial phagocytosis. Hum Mutat. 2010;31(9):1069–79.

    Article  PubMed  CAS  Google Scholar 

  • Gorden KB, Gorski KS, Gibson SJ, Kedl RM, Kieper WC, Qiu X, et al. Synthetic TLR agonists reveal functional differences between human TLR7 and TLR8. J Immunol. 2005;174(3):1259–68.

    Article  PubMed  CAS  Google Scholar 

  • Gosu V, Basith S, Kwon OP, Choi S. Therapeutic applications of nucleic acids and their analogues in Toll-like receptor signaling. Molecules. 2012;17(11):13503–29.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Gu L, Zhou J, Tan J, Yang J, Shen T, Jiang H, et al. Association of TLR8 gene rs3764880 polymorphisms with susceptibility and lipid metabolism- and inflammation response-related quantitative traits of ischemic stroke in southern Chinese Han male population. J Neurol Sci. 2016;370:94–9.

    Article  PubMed  CAS  Google Scholar 

  • Heil F, Hemmi H, Hochrein H, Ampenberger F, Kirschning C, Akira S, et al. Species-specific recognition of single-stranded RNA via toll-like receptor 7 and 8. Science. 2004;303(5663):1526–9.

    Article  PubMed  CAS  Google Scholar 

  • Hornung V, Rothenfusser S, Britsch S, Krug A, Jahrsdorfer B, Giese T, et al. Quantitative expression of toll-like receptor 1-10 mRNA in cellular subsets of human peripheral blood mononuclear cells and sensitivity to CpG oligodeoxynucleotides. J Immunol. 2002;168(9):4531–7.

    Article  PubMed  CAS  Google Scholar 

  • Ignatz-Hoover JJ, Wang H, Moreton SA, Chakrabarti A, Agarwal MK, Sun K, et al. The role of TLR8 signaling in acute myeloid leukemia differentiation. Leukemia. 2015;29(4):918–26.

    Article  PubMed  CAS  Google Scholar 

  • Ishii N, Funami K, Tatematsu M, Seya T, Matsumoto M. Endosomal localization of TLR8 confers distinctive proteolytic processing on human myeloid cells. J Immunol. 2014;193(10):5118–28.

    Article  PubMed  CAS  Google Scholar 

  • Itoh H, Tatematsu M, Watanabe A, Iwano K, Funami K, Seya T, et al. UNC93B1 physically associates with human TLR8 and regulates TLR8-mediated signaling. PLoS One. 2011;6(12):e28500.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Jurk M, Heil F, Vollmer J, Schetter C, Krieg AM, Wagner H, et al. Human TLR7 or TLR8 independently confer responsiveness to the antiviral compound R-848. Nat Immunol. 2002;3(6):499.

    Article  PubMed  CAS  Google Scholar 

  • Kaczanowska S, Joseph AM, Davila E. TLR agonists: our best frenemy in cancer immunotherapy. J Leukoc Biol. 2013;93(6):847–63.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kawasaki T, Kawai T. Toll-like receptor signaling pathways. Front Immunol. 2014;5:461.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kornblit B, Enevold C, Wang T, Spellman S, Haagenson M, Lee SJ, et al. Toll-like receptor polymorphisms in allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2015;21(2):259–65.

    Article  PubMed  CAS  Google Scholar 

  • Kruger A, Oldenburg M, Chebrolu C, Beisser D, Kolter J, Sigmund AM, et al. Human TLR8 senses UR/URR motifs in bacterial and mitochondrial RNA. EMBO Rep. 2015;16(12):1656–63.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Larange A, Antonios D, Pallardy M, Kerdine-Romer S. TLR7 and TLR8 agonists trigger different signaling pathways for human dendritic cell maturation. J Leukoc Biol. 2009;85(4):673–83.

    Article  PubMed  CAS  Google Scholar 

  • Lee CC, Avalos AM, Ploegh HL. Accessory molecules for Toll-like receptors and their function. Nat Rev Immunol. 2012;12(3):168–79.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lee BL, Moon JE, Shu JH, Yuan L, Newman ZR, Schekman R, et al. UNC93B1 mediates differential trafficking of endosomal TLRs. Elife. 2013;2:e00291.

    Article  PubMed  PubMed Central  Google Scholar 

  • Li B, Ma HM, Wang XX, Li YQ, Liu HB, Hong LZ, et al. Expression and significance of toll-like receptors 7 and 8 in brain and lung tissues of death cases caused by EV71 infection. Zhongguo Dang Dai Er Ke Za Zhi. 2015;17(10):1051–5.

    PubMed  CAS  Google Scholar 

  • Li T, He X, Jia H, Chen H, Zeng S, Fang Y, Jin Q, Jing Z. Molecular cloning and functional characterization of murine toll-like receptor 8. Mol Med Rep. 2016;13:1119–26.

    Article  PubMed  CAS  Google Scholar 

  • Makni-Maalej K, Marzaioli V, Boussetta T, Belambri SA, Gougerot-Pocidalo MA, Hurtado-Nedelec M, et al. TLR8, but not TLR7, induces the priming of the NADPH oxidase activation in human neutrophils. J Leukoc Biol. 2015;97(6):1081–7.

    Article  PubMed  CAS  Google Scholar 

  • Miyake K, Shibata T, Ohto U, Shimizu T. Emerging roles of the processing of nucleic acids and Toll-like receptors in innate immune responses to nucleic acids. J Leukoc Biol. 2016. https://doi.org/10.1189/jlb.4MR0316-108R.

    Article  PubMed  Google Scholar 

  • Netea MG, Wijmenga C, O’Neill LA. Genetic variation in Toll-like receptors and disease susceptibility. Nat Immunol. 2012;13(6):535–42.

    Article  PubMed  CAS  Google Scholar 

  • Papaioannou AI, Spathis A, Kostikas K, Karakitsos P, Papiris S, Rossios C. The role of endosomal toll-like receptors in asthma. Eur J Pharmacol. 2016. https://doi.org/10.1016/j.ejphar.2016.09.033.

    Article  PubMed  Google Scholar 

  • Paul AM, Acharya D, Le L, Wang P, Stokic DS, Leis AA, et al. TLR8 couples SOCS-1 and restrains TLR7-mediated antiviral immunity, exacerbating West Nile virus infection in mice. J Immunol. 2016;197(11):4425–35.

    Article  PubMed  CAS  Google Scholar 

  • Pelka K, Phulphagar K, Zimmermann J, Stahl R, Schmid-Burgk JL, Schmidt T, et al. Cutting edge: the UNC93B1 tyrosine-based motif regulates trafficking and TLR responses via separate mechanisms. J Immunol. 2014;193(7):3257–61.

    Article  PubMed  CAS  Google Scholar 

  • Peng G, Guo Z, Kiniwa Y, Voo KS, Peng W, Fu T, et al. Toll-like receptor 8-mediated reversal of CD4+ regulatory T cell function. Science. 2005;309(5739):1380–4.

    Article  PubMed  CAS  Google Scholar 

  • Salie M, Daya M, Lucas LA, Warren RM, van der Spuy GD, van Helden PD, et al. Association of toll-like receptors with susceptibility to tuberculosis suggests sex-specific effects of TLR8 polymorphisms. Infect Genet Evol. 2015;34:221–9.

    Article  PubMed  CAS  Google Scholar 

  • Schurz H, Daya M, Moller M, Hoal EG, Salie M. TLR1, 2, 4, 6 and 9 variants associated with tuberculosis susceptibility: a systematic review and meta-analysis. PLoS One. 2015;10(10):e0139711.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Song DH, Lee JO. Sensing of microbial molecular patterns by Toll-like receptors. Immunol Rev. 2012;250(1):216–29.

    Article  PubMed  CAS  Google Scholar 

  • Song GG, Lee YH. Association between BLK polymorphisms and susceptibility to SLE: a meta-analysis. Z Rheumatol. 2016. https://doi.org/10.1007/s00393-016-0072-8.

    Article  PubMed  Google Scholar 

  • Sun Q, Zhang Q, Xiao HP, Bai C. Toll-like receptor polymorphisms and tuberculosis susceptibility: A comprehensive meta-analysis. J Huazhong Univ Sci Technolog Med Sci. 2015;35(2):157–68.

    Article  PubMed  CAS  Google Scholar 

  • Tang J, Zhan L, Qin C. Inhibition of TLR8 mediated signaling promotes BCG induced apoptosis in THP-1 cells. Microb Pathog. 2016;93:78–82.

    Article  PubMed  CAS  Google Scholar 

  • Tanji H, Ohto U, Shibata T, Miyake K, Shimizu T. Structural reorganization of the Toll-like receptor 8 dimer induced by agonistic ligands. Science. 2013;339(6126):1426–9.

    Article  PubMed  CAS  Google Scholar 

  • Tanji H, Ohto U, Shibata T, Taoka M, Yamauchi Y, Isobe T, et al. Toll-like receptor 8 senses degradation products of single-stranded RNA. Nat Struct Mol Biol. 2015;22(2):109–15.

    Article  PubMed  CAS  Google Scholar 

  • Tanji H, Ohto U, Motoi Y, Shibata T, Miyake K, Shimizu T. Autoinhibition and relief mechanism by the proteolytic processing of Toll-like receptor 8. Proc Natl Acad Sci USA. 2016;113(11):3012–7.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Thada S, Valluri VL, Gaddam SL. Influence of Toll-like receptor gene polymorphisms to tuberculosis susceptibility in humans. Scand J Immunol. 2013;78(3):221–9.

    Article  PubMed  CAS  Google Scholar 

  • Tian T, Sun D, Wang P, Wang H, Bai X, Yang X, et al. Roles of Toll-like receptor 7 and 8 in prevention of intrauterine transmission of hepatitis B virus. Cell Physiol Biochem. 2015;37(2):445–53.

    Article  PubMed  CAS  Google Scholar 

  • Tran NL, Manzin-Lorenzi C, Santiago-Raber ML. Toll-like receptor 8 deletion accelerates autoimmunity in a mouse model of lupus through a Toll-like receptor 7-dependent mechanism. Immunology. 2015;145(1):60–70.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Wang J, Shao Y, Bennett TA, Shankar RA, Wightman PD, Reddy LG. The functional effects of physical interactions among Toll-like receptors 7, 8, and 9. J Biol Chem. 2006;281(49):37427–34.

    Article  PubMed  CAS  Google Scholar 

  • Wang CH, Eng HL, Lin KH, Liu HC, Chang CH, Lin TM. Functional polymorphisms of TLR8 are associated with hepatitis C virus infection. Immunology. 2014b;141(4):540–8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Wang CM, Chang SW, Wu YJ, Lin JC, Ho HH, Chou TC, et al. Genetic variations in Toll-like receptors (TLRs 3/7/8) are associated with systemic lupus erythematosus in a Taiwanese population. Sci Rep. 2014a;4:3792.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Willie B, Hall NB, Stein CM, Jurevic RJ, Weinberg A, Mehlotra RK, et al. Association of Toll-like receptor polymorphisms with HIV status in North Americans. Genes Immun. 2014;15(8):569–77.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Wu L, Hu Y, Li D, Jiang W, Xu B. Screening toll-like receptor markers to predict latent tuberculosis infection and subsequent tuberculosis disease in a Chinese population. BMC Med Genet. 2015;16:19.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zhang Q, Qian FH, Yin XW, Cao Q, Bai JL, Du Q, et al. Associations of Toll-like receptor 7 and 8 polymorphisms with asthma and asthma-related phenotypes in a Chinese Han population. Iran J Allergy Asthma Immunol. 2015;14(6):569–80.

    PubMed  Google Scholar 

  • Zimmermann M, Arruda-Silva F, Bianchetto-Aguilera F, Finotti G, Calzetti F, Scapini P, et al. IFNalpha enhances the production of IL-6 by human neutrophils activated via TLR8. Sci Rep. 2016;6:19674.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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Correspondence to Jorge L. Cervantes .

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Cervantes, J.L., Maulén, N., Chai, HH. (2018). TLR8. In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, Cham. https://doi.org/10.1007/978-3-319-67199-4_101876

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