Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

Toll-Like Receptor 9

  • Felipe Francisco TuonEmail author
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_14



Historical Background

Toll receptors are transmembrane proteins that are evolutionarily conserved. These receptors were first recognized in Drosophila, as an essential molecule for embryogenic patterning (Anderson 2000).

Activation of these receptors in Drosophila initiates an intracellular kinase cascade that produces a translocation of transcription factors from cytoplasm to nucleus. These factors activate a variety of inflammatory mediators and cytokines, initiating an immune response (Imler and Hoffmann 2000).

Considering these facts, some researchers began a search for toll-related proteins in humans. In 1997, they identified the first human homologue, initially termed “human toll” and subsequently termed  TLR4 (Medzhitov et al. 1997). After this, more toll-like receptors were discovered, as TLR1, TLR2, TLR3,  TLR5, and TLR6.

In 2000, Du et al. examined the human genomic sequence database in an effort to identify novel TLRs (Du et al. 2000). He found more three...

This is a preview of subscription content, log in to check access.


  1. Anderson KV. Toll signaling pathways in the innate immune response. Curr Opin Immunol. 2000;12:13–9.PubMedPubMedCentralCrossRefGoogle Scholar
  2. Baeuerle PA, Baltimore D. NF-kB: ten years after. Cell. 1996;87:13–20.PubMedPubMedCentralCrossRefGoogle Scholar
  3. Barton GM, Kagan JC, Medzhitov R. Intracellular localization of Toll-like receptor 9 prevents recognition of self DNA but facilitates access to viral DNA. Nat Immunol. 2006;7:49–56.PubMedPubMedCentralCrossRefGoogle Scholar
  4. Bauer S, Kirschning CJ, Hacker H, et al. Human TLR9 confers responsiveness to bacterial DNA via species-specific CpG motif recognition. Proc Natl Acad Sci USA. 2001;98:9237–42.PubMedPubMedCentralCrossRefGoogle Scholar
  5. Chuang TH, Ulevitch RJ. Cloning and characterization of a sub-family of human toll-like receptors: hTLR7, hTLR8 and hTLR9. Eur Cytokine Netw. 2000;11:372–8.PubMedPubMedCentralGoogle Scholar
  6. Du X, Poltorak A, Wei Y, Beutler B. Three novel mammalian toll-like receptors: gene structure, expression, and evolution. Eur Cytokine Netw. 2000;11:362–71.PubMedPubMedCentralGoogle Scholar
  7. Gangloff M, Gay NJ. Baseless assumptions: activation of TLR9 by DNA. Immunity. 2008;28:293–4.PubMedPubMedCentralCrossRefGoogle Scholar
  8. Hacker H, Mischak H, Hacker G, et al. Cell type-specific activation of mitogen-activated protein kinases by CpG-DNA controls interleukin-12 release from antigen-presenting cells. EMBO J. 1999;18:6973–82.PubMedPubMedCentralCrossRefGoogle Scholar
  9. Hacker H, Vabulas RM, Takeuchi O, Hoshino K, Akira S, Wagner H. Immune cell activation by bacterial CpG-DNA through myeloid differentiation marker 88 and tumor necrosis factor receptorassociated factor (TRAF)6. J Exp Med. 2000;192:595–600.PubMedPubMedCentralCrossRefGoogle Scholar
  10. Hemmi H, Takeuchi O, Kawai T, Kaisho T, Sato S, Sanjo HA. Toll-like receptor recognizes bacterial DNA. Nature. 2000;408:740–5.PubMedPubMedCentralCrossRefGoogle Scholar
  11. Hickey MJ, Williams SA, Roth GJ. Human platelet glycoprotein IX: an adhesive prototype of leucine-rich glycoproteins with flank-center-flank structures. Proc Natl Acad Sci USA. 1989;86:6773–7.PubMedPubMedCentralCrossRefGoogle Scholar
  12. Imler JL, Hoffmann JA. Signaling mechanisms in the antimicrobial host defense of Drosophila. Curr Opin Microbiol. 2000;3:16–22.PubMedPubMedCentralCrossRefGoogle Scholar
  13. Krieg AM. Antiinfective applications of toll-like receptor 9 agonists. Proc Am Thorac Soc. 2007;4:289–94.PubMedPubMedCentralCrossRefGoogle Scholar
  14. Krieg AM. Toll-like receptor 9 (TLR9) agonists in the treatment of cancer. Oncogene. 2008;27:161–7.PubMedPubMedCentralCrossRefGoogle Scholar
  15. Krieg AM, Vollmer J. Toll-like receptors 7, 8, and 9: linking innate immunity to autoimmunity. Immunol Rev. 2007;220:251–69.PubMedPubMedCentralCrossRefGoogle Scholar
  16. Medzhitov R, Preston-Hurlburt P, Janeway Jr CAA. human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature. 1997;388:394–7.PubMedPubMedCentralCrossRefGoogle Scholar
  17. Schnare M, Holt AC, Takeda K, Akira S, Medzhitov R. Recognition of CpG DNA is mediated by signaling pathways dependent on the adaptor protein MyD88. Curr Biol. 2000;10:1139–42.PubMedPubMedCentralCrossRefGoogle Scholar
  18. Sun S, Rao NL, Venable J, Thurmond R, Karlsson L. TLR7/9 antagonists as therapeutics for immune-mediated inflammatory disorders. Inflamm Allergy Drug Targets. 2007;6:223–35.PubMedPubMedCentralCrossRefGoogle Scholar
  19. Tuon FF, Fernandes ER, Duarte MI, Amato VS. The expression of TLR2, TLR4 and TLR9 in the epidermis of patients with cutaneous leishmaniasis. J Dermatol Sci. 2010a;59:55–7.PubMedPubMedCentralCrossRefGoogle Scholar
  20. Tuon FF, Fernandes ER, Pagliari C, Duarte MI, Amato VS. The expression of TLR9 in human cutaneous leishmaniasis is associated with granuloma. Parasite Immunol. 2010b;32:769–72.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Division of Infectious and Parasitic DiseasesHospital Universitario Evangelico de CuritibaCuritibaBrazil