Encyclopedia of Signaling Molecules

2012 Edition
| Editors: Sangdun Choi

Toll-Like Receptor 3

  • Aisha Qasim Butt
  • Sinéad M. Miggin
Reference work entry
DOI: https://doi.org/10.1007/978-1-4419-0461-4_607


Historical Background

The innate immune system of mammals is equipped with various kinds of cells, such as macrophages and dendritic cells (DCs), which provides the first line of defense to the host in recognizing various kinds of pathogens. These cells have developed different classes of protein based receptors for recognizing numerous kinds of pathogen associated molecular patterns (PAMPs) (Miggin and O’Neill 2006). These different classes of pathogen recognition receptors (PRRs) includes, Membrane bound PRRs such as Toll-like receptors (TLRs), Receptor kinases, Mannose receptors and Cytoplasmic PRRssuch as Nucleotide oligomerization domain (NOD) receptors, the Retinoic acid inducible gene I (RIG-I)-like receptor (RLR) family, and the recently described AIM2 and DAI cytosolic DNA receptors. All these receptor proteins play a crucial role in “danger” recognition and induction of the innate immune responses against a variety of bacterial and viral...

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


  1. Bell JK, Askins J, Hall PR, Davies DR, Segal DM. The dsRNA binding site of human Toll-like receptor 3. Proc Natl Acad Sci USA. 2006;103:8792–7.PubMedGoogle Scholar
  2. Botos I, Liu L, Wang Y, Segal DM, Davies DR. The toll-like receptor 3:dsRNA signaling complex. Biochim Biophys Acta. 2009;1789:667–74.PubMedGoogle Scholar
  3. Carty M, Goodbody R, Schroder M, Stack J, Moynagh PN, Bowie AG. The human adaptor SARM negatively regulates adaptor protein TRIF-dependent Toll-like receptor signaling. Nat Immunol. 2006;7:1074–81.PubMedGoogle Scholar
  4. Cheng YS, Xu F. Anticancer function of polyinosinic-polycytidylic acid. Cancer Biol Ther. 2010;10:1219–23.PubMedGoogle Scholar
  5. de Bouteiller O, Merck E, Hasan UA, Hubac S, Benguigui B, Trinchieri G, et al. Recognition of double-stranded RNA by human toll-like receptor 3 and downstream receptor signaling requires multimerization and an acidic pH. J Biol Chem. 2005;280:38133–45.PubMedGoogle Scholar
  6. Funami K, Matsumoto M, Oshiumi H, Akazawa T, Yamamoto A, Seya T. The cytoplasmic ‘linker region’ in Toll-like receptor 3 controls receptor localization and signaling. Int Immunol. 2004;16:1143–54.PubMedGoogle Scholar
  7. Gauzzi C, Del Corno M, Gessani S. Dissecting TLR3 signalling in dendritic cells. Immunobiology. 2010;215:713–23.PubMedGoogle Scholar
  8. Jin B, Sun T, Yu XH, Liu CQ, Yang YX, Lu P, et al. Immunomodulatory effects of dsRNA and its potential as vaccine adjuvant. J Biomed Biotechnol. 2010;2010:690438.PubMedGoogle Scholar
  9. Johnson AC, Li X, Pearlman E. MyD88 functions as a negative regulator of TLR3/TRIF-induced corneal inflammation by inhibiting activation of c-Jun N-terminal kinase. J Biol Chem. 2008;283:3988–96.PubMedGoogle Scholar
  10. Kenny EF, Talbot S, Gong M, Golenbock DT, Bryant CE, O’Neill LA. MyD88 adaptor-like is not essential for TLR2 signaling and inhibits signaling by TLR3. J Immunol. 2009;183:3642–51.PubMedGoogle Scholar
  11. Kumar H, Kawai T, Akira S. Pathogen recognition in the innate immune response. Biochem J. 2009;420:1–16.PubMedGoogle Scholar
  12. Miggin SM, O’Neill LA. New insights into the regulation of TLR signaling. J Leukoc Biol. 2006;80:220–6.PubMedGoogle Scholar
  13. Nomura N, Nagase T, Miyajima N, Sazuka T, Tanaka A, Sato S, et al. Prediction of the coding sequences of unidentified human genes. II. The coding sequences of 40 new genes (KIAA0041-KIAA0080) deduced by analysis of cDNA clones from human cell line KG-1 (supplement). DNA Res. 1994;1:251–62.PubMedGoogle Scholar
  14. Oganesyan G, Saha SK, Guo B, He JQ, Shahangian A, Zarnegar B, et al. Critical role of TRAF3 in the Toll-like receptor-dependent and -independent antiviral response. Nature. 2006;439:208–11.PubMedGoogle Scholar
  15. Sasai M, Tatematsu M, Oshiumi H, Funami K, Matsumoto M, Hatakeyama S, et al. Direct binding of TRAF2 and TRAF6 to TICAM-1/TRIF adaptor participates in activation of the Toll-like receptor 3/4 pathway. Mol Immunol. 2010;47:1283–91.PubMedGoogle Scholar
  16. Schröder M, Baran M, Bowie AG. Viral targeting of DEAD box protein 3 reveals its role in TBK1/IKKe-mediated IRF activation. EMBO J. 2008;27:2147–57.PubMedGoogle Scholar
  17. Siednienko J, Miggin SM. Expression analysis of the Toll-like receptors in human peripheral blood mononuclear cells. Methods Mol Biol. 2009;517:3–14.PubMedGoogle Scholar
  18. Siednienko J, Halle A, Nagpal K, Golenbock DT, Miggin SM. TLR3-mediated IFN-beta gene induction is negatively regulated by the TLR adaptor MyD88 adaptor-like. Eur J Immunol. 2010;40:3150–60.PubMedGoogle Scholar
  19. Siednienko J, Gajanayake T, Fitzgerald KA, Moynagh P, Miggin SM. Absence of MyD88 results in enhanced TLR3-dependent phosphorylation of IRF3 and increased IFN-(beta) and RANTES production. J Immunol. 2011;186:2514–22.PubMedGoogle Scholar
  20. Vercammen E, Staal J, Beyaert R. Sensing of viral infection and activation of innate immunity by toll-like receptor 3. Clin Microbiol Rev. 2008;21:13–25.PubMedGoogle Scholar
  21. Yamamoto M, Takeda K. Current views of toll-like receptor signaling pathways. Gastroenterol Res Pract. 2010;2010:240365.PubMedGoogle Scholar
  22. Zhou Y, Wang X, Liu M, Hu Q, Song L, Ye L, et al. A critical function of toll-like receptor-3 in the induction of anti-human immunodeficiency virus activities in macrophages. Immunology. 2010;131:40–9.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Department of Biology, Institute of ImmunologyNational University of Ireland MaynoothMaynoothIreland