Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

TLR7

  • Sandy R. Larson
  • Shaikh Muhammad Atif
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_101511

Synonyms

Historical Background

Beutler group identified TLR7 along with TLR8 and TLR9 within an established genomic database in the year 2000 (Du et al. 2000). TLR7 was evolved from common ancestral gene about 150 million years ago and was found to be X linked (Du et al. 2000). In 2002, synthetic chemical imiquimod was reported to be sense by TLR7, which was characterized as another antiviral TLR (Hemmi et al. 2002). Later in 2004, two groups independently identified TLR7 as a sensor of single-stranded viral RNA (Diebold et al. 2004; Heil et al. 2004). There are several synthetic compounds belonging to imidazoquinoline family, which have been identified as TLR7 and/or TLR8 agonists (Diebold et al. 2004). Among these agonists, the lead compound imiquimod exerts strong antiviral and antitumoral activities and is being marketed for the treatment of external genital warts caused by human papillomavirus (Wolf et al. 2003).

Introduction

Pattern recognition receptors are...

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References

  1. Akira S, Takeda K. Toll-like receptor signalling. Nat Rev Immunol. 2004;4(7):499–511.PubMedPubMedCentralCrossRefGoogle Scholar
  2. Christensen SR, Shupe J, Nickerson K, Kashgarian M, Flavell RA, Shlomchik MJ. Toll-like receptor 7 and TLR9 dictate autoantibody specificity and have opposing inflammatory and regulatory roles in a murine model of lupus. Immunity. 2006;25(3):417–28.PubMedPubMedCentralCrossRefGoogle Scholar
  3. Diebold SS, Kaisho T, Hemmi H, Akira S.Reis e Sousa C. Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA. Science. 2004;303(5663):1529–31.PubMedPubMedCentralCrossRefGoogle Scholar
  4. Du X, Poltorak A, Wei Y, Beutler B. Three novel mammalian toll-like receptors: gene structure, expression, and evolution. Eur Cytokine Netw. 2000;11(3):362–71.PubMedPubMedCentralGoogle Scholar
  5. Ewald SE, Lee BL, Lau L, Wickliffe KE, Shi GP, Chapman HA, Barton GM. The ectodomain of Toll-like receptor 9 is cleaved to generate a functional receptor. Nature. 2008;456(7222):658–62.PubMedPubMedCentralCrossRefGoogle Scholar
  6. Ewald SE, Engel A, Lee J, Wang M, Bogyo M, Barton GM. Nucleic acid recognition by Toll-like receptors is coupled to stepwise processing by cathepsins and asparagine endopeptidase. J Exp Med. 2011;208(4):643–51.PubMedPubMedCentralCrossRefGoogle Scholar
  7. Gehrig S, Eberle ME, Botschen F, Rimbach K, Eberle F, Eigenbrod T, Kaiser S, Holmes WM, Erdmann VA, Sprinzl M, Bec G, Keith G, Dalpke AH, Helm M. Identification of modifications in microbial, native tRNA that suppress immunostimulatory activity. J Exp Med. 2012;209(2):225–33.PubMedPubMedCentralCrossRefGoogle Scholar
  8. Gentile F, Deriu MA, Licandro G, Prunotto A, Danani A, Tuszynski JA. Structure based modeling of small molecules binding to the TLR7 by atomistic level simulations. Molecules. 2015;20(5):8316–40.PubMedPubMedCentralCrossRefGoogle Scholar
  9. Green NM, Laws A, Kiefer K, Busconi L, Kim YM, Brinkmann MM, Trail EH, Yasuda K, Christensen SR, Shlomchik MJ, Vogel S, Connor JH, Ploegh H, Eilat D, Rifkin IR, van Seventer JM, Marshak-Rothstein A. Murine B cell response to TLR7 ligands depends on an IFN-β feedback loop. J Immunol. 2009;183(3):1569–76.PubMedPubMedCentralCrossRefGoogle Scholar
  10. Guiducci C, Ghirelli C, Marloie-Provost MA, Matray T, Coffman RL, Liu YJ, Barrat FJ, Soumelis V. PI3K is critical for the nuclear translocation of IRF-7 and type I IFN production by human plasmacytoid predendritic cells in response to TLR activation. J Exp Med. 2008;205(2):315–22.PubMedPubMedCentralCrossRefGoogle Scholar
  11. Hayashi T, Gray CS, Chan M, Tawatao RI, Ronacher L, McGargill MA, Datta SK, Carson DA, Corr M. Prevention of autoimmune disease by induction of tolerance to Toll-like receptor 7. Proc Natl Acad Sci USA. 2009;106(8):2764–9.PubMedPubMedCentralCrossRefGoogle Scholar
  12. Heil F, Hemmi H, Hochrein H, Ampenberger F, Kirschning C, Akira S, Lipford G, Wagner H, Bauer S. Species-specific recognition of single stranded RNA via Toll-like receptor 7 and 8. Science. 2004;303(5663):1526–9.PubMedCrossRefGoogle Scholar
  13. Hemmi H, Kaisho T, Takeuchi O, Sato S, Sanjo H, Hoshino K, Horiuchi T, Tomizawa H, Takeda K, Akira S. Small anti-viral compounds activate immune cells via the TLR7 MyD88-dependent signaling pathway. Nat Immunol. 2002;3(2):196–200.PubMedPubMedCentralCrossRefGoogle Scholar
  14. Jeisy-Scott V, Kim JH, Davis WG, Cao W, Katz JM, Sambhara S. TLR7 recognition is dispensable for influenza virus A infection but important for the induction of hemagglutinin-specific antibodies in response to the 2009 pandemic split vaccine in mice. J Virol. 2012;86(20):10988–98.PubMedPubMedCentralCrossRefGoogle Scholar
  15. Jöckel S, Nees G, Sommer R, Zhao Y, Cherkasov D, Hori H, Ehm G, Schnare M, Nain M, Kaufmann A, Bauer S. The 2′-O-methylation status of a single guanosine controls transfer RNA-mediated Toll-like receptor 7 activation or inhibition. J Exp Med. 2012;209(2):235–41.PubMedPubMedCentralCrossRefGoogle Scholar
  16. Kanno A, Tanimura N, Ishizaki M, Ohko K, Motoi Y, Onji M, Fukui R, Shimozato T, Yamamoto K, Shibata T, Sano S, Sugahara-Tobinai A, Takai T, Ohto U, Shimizu T, Saitoh S, Miyake K. Targeting cell surface TLR7 for therapeutic intervention in autoimmune diseases. Nat Commun. 2015;6:6119.PubMedPubMedCentralCrossRefGoogle Scholar
  17. Kawai T, Akira S. Innate immune recognition of viral infection. Nat Immunol. 2006;7(2):131–7.PubMedPubMedCentralCrossRefGoogle Scholar
  18. Kawai T, Akira S. The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat Immunol. 2010;11(5):373–84.  https://doi.org/10.1038/ni.1863.CrossRefGoogle Scholar
  19. Kim YM, Brinkmann MM, Paquet ME, Ploegh HL. UNC93B1 delivers nucleotide-sensing toll-like receptors to endolysosomes. Nature. 2008;452(7184):234–8.PubMedPubMedCentralCrossRefGoogle Scholar
  20. Lee AS, Ghoreishi M, Cheng WK, Chang TY, Zhang YQ, Dutz JP. Toll-like receptor 7 stimulation promotes autoimmune diabetes in the NOD mouse. Diabetologia. 2011;54(6):1407–16.PubMedPubMedCentralCrossRefGoogle Scholar
  21. Lund JM, Alexopoulou L, Sato A, Karow M, Adams NC, Gale NW, Iwasaki A, Flavell RA. Recognition of single-stranded RNA viruses by Toll-like receptor 7. Proc Natl Acad Sci USA. 2004;101(15):5598–603.PubMedPubMedCentralCrossRefGoogle Scholar
  22. Mancuso G, Gambuzza M, Midiri A, Biondo C, Papasergi S, Akira S, Teti G, Beninati C. Bacterial recognition by TLR7 in the lysosomes of conventional dendritic cells. Nat Immunol. 2009;10(6):587–94.  https://doi.org/10.1038/ni.1733.CrossRefPubMedGoogle Scholar
  23. Matsushima N, Tanaka T, Enkhbayar P, Mikami T, Taga M, Yamada K, Kuroki Y. Comparative sequence analysis of leucine-rich repeats (LRRs) within vertebrate toll-like receptors. BMC Genomics. 2007;8:124.PubMedPubMedCentralCrossRefGoogle Scholar
  24. Medzhitov R. Recognition of microorganisms and activation of the immune response. Nature. 2007;449(7164):819–26.PubMedPubMedCentralCrossRefGoogle Scholar
  25. Meyer T, Surber C, French LE, Stockfleth E. Resiquimod, a topical drug for viral skin lesions and skin cancer. Expert Opin Investig Drugs. 2013;22(1):149–59.PubMedPubMedCentralCrossRefGoogle Scholar
  26. Mogensen TH. Pathogen recognition and inflammatory signaling in innate immune defenses. Clin Microbiol Rev. 2009;22(2):240–73.PubMedPubMedCentralCrossRefGoogle Scholar
  27. Pisitkun P, Deane JA, Difilippantonio MJ, Tarasenko T, Satterthwaite AB, Bolland S. Autoreactive B cell responses to RNA-related antigens due to TLR7 gene duplication. Science. 2006;312(5780):1669–72.PubMedCrossRefGoogle Scholar
  28. Ramirez-Ortiz ZG, Prasad A, Griffith JW, Pendergraft 3rd WF, Cowley GS, Root DE, Tai M, Luster AD, El Khoury J, Hacohen N, Means TK. The receptor TREML4 amplifies TLR7-mediated signaling during antiviral responses and autoimmunity. Nat Immunol. 2015;16(5):495–504.PubMedPubMedCentralCrossRefGoogle Scholar
  29. Schott E, Witt H, Neumann K, Taube S, Oh DY, Schreier E, Vierich S, Puhl G, Bergk A, Halangk J, Weich V, Wiedenmann B, Berg T. A Toll-like receptor 7 single nucleotide polymorphism protects from advanced inflammation and fibrosis in male patients with chronic HCV-infection. J Hepatol. 2007;47(2):203–11.PubMedCrossRefGoogle Scholar
  30. Shibata T, Ohto U, Nomura S, Kibata K, Motoi Y, Zhang Y, Murakami Y, Fukui R, Ishimoto T, Sano S, Ito T, Shimizu T, Miyake K. Guanosine and its modified derivatives are endogenous ligands for TLR7. Int Immunol. 2016;28(5):211–22.PubMedCrossRefGoogle Scholar
  31. Song DH, Lee JO. Sensing of microbial molecular patterns by Toll-like receptors. Immunol Rev. 2012;250(1):216–29.  https://doi.org/10.1111/j.1600-065X.2012.01167.x.CrossRefPubMedPubMedCentralGoogle Scholar
  32. Takahashi K, Shibata T, Akashi-Takamura S, Kiyokawa T, Wakabayashi Y, Tanimura N, Kobayashi T, Matsumoto F, Fukui R, Kouro T, Nagai Y, Takatsu K, Saitoh S, Miyake K. A protein associated with Toll-like receptor (TLR) 4 (PRAT4A) is required for TLR-dependent immune responses. J Exp Med. 2007;204(12):2963–76.PubMedPubMedCentralCrossRefGoogle Scholar
  33. Wolf IH, Smolle J, Binder B, Cerroni L, Richtig E, Kerl H. Topical imiquimod in the treatment of metastatic melanoma to skin. Arch Dermatol. 2003;139(3):273–6.PubMedPubMedCentralCrossRefGoogle Scholar
  34. Wonderlich ER, Barratt-Boyes SM. SIV infection of rhesus macaques differentially impacts mononuclear phagocyte responses to virus-derived TLR agonists. J Med Primatol. 2013;42(5):247–53.PubMedPubMedCentralCrossRefGoogle Scholar
  35. Zhang Z, Ohto U, Shibata T, Krayukhina E, Taoka M, Yamauchi Y, Tanji H, Isobe T, Uchiyama S, Miyake K, Shimizu T. Structural analysis reveals that Toll-like receptor 7 is a dual receptor for guanosine and single-stranded RNA. Immunity. 2016;45(4):737–48.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Department of Immunology and MicrobiologyUniversity of Colorado DenverAuroraUSA
  2. 2.Department of PediatricsNational Jewish HealthDenverUSA