Beyond dsRNA: Toll-like receptor 3 signalling in RNA-induced immune responses

Biochemical Journal

Volumn 458, Issue 2, 2014, Pages 195-201

  Tatematsu, Megumi ^a   Seya, Tsukasa ^a   Matsumoto, Misako ^a  

^a HOKKAIDO UNIVERSITY GRADUATE SCHOOL OF MEDICINE   (Japan)

Author keywords

Dendritic cell; DsRNA; Endocytosis; Innate immunity; Structured RNA; Toll like receptor (TLR); Type I interferon; Uptake receptor; Viral infection

Indexed keywords

ANIMALS; HUMANS; RNA; RNA VIRUSES; RNA, DOUBLE-STRANDED; RNA, VIRAL; SIGNAL TRANSDUCTION; TOLL-LIKE RECEPTOR 3;

EID: 84894267102     PISSN: 02646021     EISSN: 14708728     Source Type: Journal    
DOI: 10.1042/BJ20131492     Document Type: Review

References (75)

1. Janeway, Jr, C. A. and Medzhitov, R. (2002) Innate immune recognition. Annu. Rev. Immunol. 20, 197-216
2. Akira, S., Uematsu, S. and Takeuchi, O. (2006) Pathogen recognition and innate immunity. Cell 124, 783-801
3. Gurtler, C. and Bowie, A. G. (2013) Innate immune detection of microbial nucleic acids. Trends Microbiol. 21, 413-420
4. Alexopoulou, L., Holt, A. C., Medzhitov, R. and Flavell, R. A. (2001) Recognition of double stranded RNA and activation of NF-κB by Toll-like receptor 3. Nature 413, 732-738
5. Matsumoto, M., Kikkawa, S., Kohase, M., Miyake, K. and Seya, T. (2002) Establishment of monoclonal antibody against human Toll-like receptor 3 that blocks double-stranded RNA-mediated signaling. Biochem. Biophys. Res. Commun. 293, 1364-1369
6. Muzio, M., Bosisio, D., Polentarutti, N., D'amico, G., Stoppacciaro, A., Mancinelli, R., van't Veer, C., Penton-Rol, G., Ruco, L. P., Allavena, P. and Mantovani, A. (2000) Differential expression and regulation of Toll-like receptors (TLR) in human leukocytes: selective expression of TLR3 in dendritic cells. J. Immunol. 64, 5998-6004
7. Cario, E. and Podolsky, D. K. (2000) Differential alteration in intestinal epithelial cell expression of toll-like receptor 3 (TLR3) and TLR4 in inflammatory bowel disease. Infect. Immun. 68, 7010-7017
8. Matsumoto, M., Funami, K., Tanabe, M., Oshiumi, H., Shingai, M., Seto, Y., Yamamoto, A. and Seya, T. (2003) Subcellular localization of Toll-like receptor 3 in human dendritic cells. J. Immunol. 171, 3154-3162
9. Funami, K., Matsumoto, M., Oshiumi, H., Akazawa, T., Yamamoto, A. and Seya, T. (2004) The cytoplasmic 'linker region' in Toll-like receptor 3 controls receptor localization and signaling. Int. Immunol. 16, 1143-1154
10. Weber, F., Wagner, V., Rasmussen, S. B., Hartmann, R. and Paludan, S. R. (2006) Double-stranded RNA is produced by positive-stranded RNA viruses and DNA viruses but not in detectable amounts by negative-stranded RNA viruses. J. Virol. 80, 5059-5064
11. Matsumoto, M., Oshiumi, H. and Seya, T. (2011) Antiviral responses induced by the TLR3 pathway. Rev. Med. Virol. 21, 67-77
12. Oshiumi, H., Okamoto, M., Fujii, K., Kawanishi, T., Matsumoto, M., Koike, S. and Seya, T. (2011) The TLR3-TICAM-1 pathway is mandatory for innate immune responses to poliovirus infection. J. Immunol. 187, 5320-5327
13. Abe, Y., Fujii, K., Nagata, N., Takeuchi, O., Akira, S., Oshiumi, H., Matsumoto, M., Seya, T. and Koike, S. (2012) The Toll-like receptor 3-mediayed antiviral response is important for protection against poliovirus infection in poliovirus receptor transgenic mice. J. Virol. 86, 185-194
14. Negishi, H., Osawa, T., Ogami, K., Ouyang, X., Sakaguchi, S., Koshiba, R., Yanai, H., Seko, Y., Shitara, H., Bishop, K. et al. (2008) A critical link between Toll-like receptor 3 and type II interferon signaling pathways in antiviral innate immunity. Proc. Natl. Acad. Sci. U.S.A. 105, 20446-20451
15. Hardarson, H. S., Baker, J. S., Yang, Z., Purevjav, E., Huang, C. H., Alexopoulou, L, Li, N., Flavell, R. A., Bowles, N. E. and Vallejo, J. G. (2007) Toll-like receptor 3 is an essential component of the innate stress response in virus-induced cardiac injury. Am. J. Physiol. Heart Circ. Physiol. 292, 251-258
16. Pott, J., Stockinger, S., Torow, N., Smoczek, A., Lindner, C, McInerney G., Backhed, F., Baumann, U., Pabst, O., Bleich, A. and Hornef, M. W. (2012) Age-dependent TLR3 expression of the intestinal epithelium contributes to rotavirus susceptibility. PLoS Pathog. 8, e1002670
17. Guo, Y, Audry, M., Ciancanelli, M., Alsina, L, Azevedo, J., Herman, M., Anguiano, E., Sancho-Shimizu, V, Lorenzo, L, Pauwels, E. et al. (2011) Herpes simplex virus encephalitis in a patient with complete TLR3 deficiency: TLR3 is otherwise redundant in protective immunity. J. Exp. Med. 208, 2083-2098
18. Sancho-Shimizu, V., Perez de Diego, R., Lorenzo, L, Halwani, R., Alangari, A., Israelsson, E., Fabrega, S., Cardon, A., Maluenda, J., Tatematsu, M. et al. (2011) Herpes simplex encephalitis in children with autosomal recessive and dominant TRIF deficiency. J.Clin. Invest. 121, 4889-4902
19. Tabeta, K., Georgel, P., Janssen, E, Du, X., Hoebe, K., Crozat, K., Mudd, S., Shamel, L, Sovath, S., Goode, J. et al. (2004) Toll-like receptor 9 and 3 as essential components of innate immune defense against mouse cytomegalovirus infection. Proc. Natl. Acad. Sci. U.S.A. 101, 3516-3521
20. Wang, T, Town, T, Alexopoulou, L, Anderson, J. F., Fikrig, E. and Flavell, R. A. (2004) Toll-like receptor 3 mediates West Nile virus entry into the brain causing lethal encephalitis. Nat. Med. 10, 1366-1373
21. Hutchens, M., Luker, K. E., Sottile, P., Sonstein, J., Lukacs, N. W., Nuñez, G., Curtis, J. L. and Luker, G. D. (2008) TLR3 increases disease morbidity and mortality from vaccinia infection. J. Immunol. 180, 483-491
22. Le Goffic, R., Balloy, V., Lagranderie, M., Alexopoulou, L, Escriou, N., Flavell, R. A., Chignard, M. and Si-Tahar, M. (2006) Detrimental contribution of the Toll-like receptor (TLR) 3 to influenza A virus-induced acute pneumonia. PLos Pathog. 2, 526-535
23. Gowen, B. B., Hoopes, J. D., Wong, M-H., Jung, K. H., Isakson, K. C, Alexopoulou, L, Flavell, R. A. and Sidwell, R. W. (2006) TLR3 deletion limits mortality and disease severity due to phlebovirus infection. J. Immunol. 177, 6301-6307
24. Kariko, K., Ni, H., Capodici, J., Lamphier, M. and Weissman, D. (2004) mRNA is an endogenous ligand for Toll-like receptor 3. J. Biol. Chem. 279, 12542-12550
25. Cavassani, K. A., Ishii, M., Wen, H., Schaller, M. A., Lincoln, P. M., Lukacs, N. W., Hogaboam, C. M. and Kunkel, S. L. (2008) TLR3 is an endogenous sensor of tissue necrosis during acute inflammatory events. J. Exp. Med. 205, 2609-2621
26. Tatematsu, M., Nishikawa, F, Seya, T. and Matsumoto, M. (2013) Toll-like receptor 3 recognizes incomplete stem structures in single-stranded viral RNA. Nat. Commun. 4, 1833
27. Oshiumi, H., Matsumoto, M., Funami, K., Akazawa, T. and Seya, T. (2003) TICAM-1, an adaptor molecule that participates in Toll-like receptor 3-mediated interferon-^ induction. Nat. Immunol. 4, 161-167
28. Yamamoto, M., Sato, S., Hemmi, H., Hoshino, K, Kaisho, T, Sanjo, H., Takeuchi, O., Sugiyama, M., Okabe, M., Takeda, K. and Akira, S. (2003) Role of adaptor TRIF in the MyD88-independent Toll-like receptor signaling pathway. Science 301, 640-643
29. Hornung, V., Ellegast, J., Kim, S., Brzózka, K., Jung, A., Kato, H., Poeck, H., Akira, S., Conzelmann, K. K., Schlee, M. et al. (2006) 5'-Triphosphate RNA is the ligand for RIG-I. Science 314, 994-997
30. Pichlmair, A., Schulz, O., Tan, C. P., Naslund, T. I., Liljeström, P., Weber, F and Reis e Sousa, C. (2006) RIG-I-mediated anti-viral responses to single-stranded RNA bearing 5'-phosphates. Science 314, 997-1001
31. Okahira, S., Nishikawa, F, Nishikawa, S., Akazawa, T, Seya, T. and Matsumoto, M. (2005) Interferon-^ induction through Toll-like receptor 3 depends on double-stranded RNA structure. DNA Cell Biol. 24, 614-623
32. Bell, J. K., Mullen, G. E. D., Leifer, C. A., Mazzoni, A., Davies, D. R. and Segal, D. M. (2003) Leucine-rich repeats and pathogen recognition in Toll-like receptors. Trends Immunol. 24, 528-533
33. Choe, J., Kelker, M. S. and Wilson, I. A. (2005) Crystal structure of human Toll-like receptor 3 (TLR3) ectodomain. Science 309, 581-585
34. Bell, J. K., Botos, I., Hall, P. R., Askins, J., Shiloach, J., Segal, D. M. and Davies, D. R. (2005) The molecular structure of the Toll-like receptor 3 ligand-binding domain. Proc. Natl. Acad. Sci. U.S.A. 102, 10976-10980
35. Fukuda, K., Watanabe, T, Tokisue, T, Tsujita, T, Nishikawa, S., Hasegawa, T, Seya, T. and Matsumoto, M. (2008) Modulation of double-stranded RNA recognition by the N-terminal histidine-rich region of the human Toll-like receptor 3. J. Biol. Chem. 283, 22787-22794
36. Pirher, N., Ivicak, K., Pohar, J., Bencina, M. and Jerala, R. (2008) A second binding site for double-stranded RNA in TLR3 and consequences for interferon activation. Nat. Struct. Mol. Biol. 15, 761-763
37. Leonard, J. N., Ghirlando, R., Askins, J., Bell, J. K., Margulies, D. H., Davies, D. R. and Segal, D. M. (2008) The TLR3 signaling complex forms by cooperative receptor dimerization. Proc. Natl. Acad. Sci. U.S.A. 105, 258-263
38. Liu, L., Botos, I., Wang, Y., Leonard, J. N., Shiloach, J., Segal, D. M. and Davies, D. R. (2008) Structural basis of Toll-like receptor 3 signaling with double-stranded RNA. Science 320, 379-381
39. Wang, Y., Liu, L., Davies, D. R. and Segal, D. M. (2010) Dimerization of Toll-like receptor 3 (TLR3) is required for ligand binding. J. Biol. Chem. 285, 36836-3641
40. Takada, E., Okahira, S., Sasai, M., Funami, K., Seya, T. and Matsumoto, M. (2007) C-terminal LRRs of human Toll-like receptor 3 control receptor dimerization and signal transmission. Mol. Immunol. 44, 3633-3640
41. Jelinek, I., Leonard, J. N., Price, G. E., Brown, K. N., Meyer-Manlapat, A., Goldsmith, P. K., Wang, Y., Venzon, D., Epstein, S. L. and Segal, D. M. (2011) TLR3-specific double-stranded RNA oligonucleotide adjuvants induce dendritic cell cross-presentation, CTL responses, and antiviral protection. J. Immunol. 186, 2422-2429
42. Bernard, J. J., Cowing-Zitron, C., Nakatsuji, T., Muehleisen, B., Muto, J., Borkowski, A. W., Martinez, L., Greidinger, E. L., Yu, B. D. and Gallo, R. L. (2012) Ultraviolet radiation damages self noncoding RNA and is detected by TLR3. Nat. Med. 18, 1286-1291
43. Itoh, K., Watanabe, A., Funami, K., Seya, T. and Matsumoto, M. (2008) The clathrin-mediated endocytic pathway participates in dsRNA-induced IFN-β production. J. Immunol. 181, 5522-5529
44. Watanabe, A., Tatematsu, M., Saeki, K., Shibata, S., Shime, H., Yoshimura, A., Obuse, C., Seya, T. and Matsumoto, M. (2011) Raftlin is involved in the nucleocapture complex to induce poly(I:C)-mediated TLR3 activation. J. Biol. Chem. 286, 10702-10711
45. Rana, T. M. (2007) Illuminating the silence: understanding the structure and function of small RNAs. Nat. Rev. Mol. Cell Biol. 8, 23-36
46. Cisse, I. I., Kim, H. and Ha, T. (2012) A rule of seven in Watson-Crick base-pairing of mismatched sequences. Nat. Struct. Mol. Biol. 19, 623-627
47. Ewald, S. E., Engel, A., Lee, J., Wang, M., Bogyo, M. and Barton, G. M. (2011) Nucleic acid recognition by Toll-like receptors is coupled to stepwise processing by cathepsins and asparagine endopeptidase. J. Exp. Med. 208, 643-651
48. Garcia-Cattaneo, A., Gobert, F. X., Müller, M., Toscano, F., Flores, M., Lescure, A., Del Nery, E. and Benaroch, P. (2012) Cleavage of Toll-like receptor 3 by cathepsins B and H is essential for signaling. Proc. Natl. Acad. Sci. U.S.A. 109, 9053-9058
49. Toscano, F., Estornes, Y., Virard, F., Garcia-Cattaneo, A., Pierrot, A., Vanbervliet, B., Bonnin, M., Ciancanelli, M. J., Zhang, S. Y., Funami, K. et al. (2013) Cleaved/associated TLR3 represents the primary form of the signaling receptor. J. Immunol. 190, 764-773
50. Qi, R., Singh, D. and Kao, C. C. (2012) Proteolytic processing regulates Toll-like receptor 3 stability and endosomal localization. J. Biol. Chem. 287, 32617-32629
51. Kato, H., Takeuchi, O., Mikamo-Satoh, E., Hirai, R., Kawai, T., Matsushita, K., Hiiragi, A., Dermody, T. S., Fujita, T. and Akira, S. (2008) Length-dependent recognition of double-stranded ribonucleic acids by retinoic acid-inducible gene-I and melanoma differentiation-associated gene 5. J. Exp. Med. 205, 1601-1610
52. Sköld, A. E., Hasan, M., Vargas, L., Saidi, H., Bosquet, N., Grand, R. L., Smith, C. I. E. and Spetz, A.-L. (2012) Single-stranded DNA oligonucleotides inhibit TLR3-mediated responses in human monocyte-derived dendritic cells and in vivoin cynomolgus macaques. Blood 120, 768-777
53. Lee, H. K. S., Dunzendorfer, K., Soldau, K. and Tobias, P. S. (2006) Double-stranded RNA-mediated TLR3 activation is enhanced by CD14. Immunity 24, 153-163
54. Limmon, G. V., Arredouani, M., McCann, K. L., Minor, R. A. C., Kobzik, L. and Imani, F. (2008) Scavenger receptor class-A is a novel cell surface receptor for double-stranded RNA. FASEB J. 22, 159-167
55. DeWitte-Orr, S. J., Collins, S. E., Bauer, C. M. T., Bowdish, D. M. and Mossma, K. L. (2010) An accessory to the 'Trinity': SR-As are essential pathogen sensors of extracellular dsRNA, mediating entry and leading to subsequent type I IFN responses. PLoS Pathog. 6, e1000829
56. Lahoud, M. H., Ahmet, F., Zhang, J. G., Meuter, S., Policheni, A. N., Kitsoulis, S., Lee, C. N., O'Keeffe, M., Sullivan, L. C., Brooks, A. G. et al. (2012) DEC-205 is a cell surface receptor for CpG oligonucleotides. Proc. Natl. Acad. Sci. U.S.A. 109, 16270-16275
57. Matsumoto, M. and Seya, T. (2008) TLR3: Interferon induction by double-stranded RNA including poly(I:C). Adv. Drug Del. Rev. 60, 805-812
58. Jongbloed, S. L., Kassianos, A. J., McDonald, K. J., Clark, G. J., Ju, X., Angel, C. E., Chen, C. J., Dunbar, P. R., Wadley, R. B., Jeet, V. et al. (2010) Human CD141 + (BDCA-3) + dendritic cells (DCs) represent a unique myeloid DC subset that cross-presents necrotic cell antigens. J. Exp. Med. 207, 1247-1260
59. Bachem, A., Güttler, S., Hartung, E., Ebstein, F., Schaefer, M., Tannert, A., Salama, A., Movassaghi, K., Opitz, C., Mages, H. W. et al. (2010) Superior antigen cross-presentation and XCR1 expression define human CD11c + CD141 + cells as homologues of mouse CD8 + dendritic cells. J. Exp. Med. 207, 1273-1281
60. Ebihara, T., Azuma, M., Oshiumi, H., Kasamatsu, J., Iwabuchi, K., Matsumoto, K., Saito, H., Taniguchi, T., Matsumoto, M. and Seya, T. (2010) Identification of a polyI:C-inducible membrane protein that participates in dendritic cell-mediated natural killer cell activation. J. Exp. Med. 207, 2675-2687
61. Seya, T. and Matsumoto, M. (2009) The extrinsic RNA-sensing pathway for adjuvant immunotherapy of cancer. Cancer Immunol. Immunother. 58, 1175-1184
62. Akazawa, T., Ebihara, T., Okuno, M., Okuda, Y., Shingai, M., Tsujimura, K., Takahashi, T., Ikawa, M., Okabe, M., Inoue, N. et al. (2007) Antitumor NK activation induced by the Toll-like receptor 3-TICAM-1 (TRIF) pathway in myeloid dendritic cells. Proc. Natl. Acad. Sci. U.S.A. 104, 252-257
63. Azuma, M., Ebihara, T., Oshiumi, H., Matsumoto, M. and Seya, T. (2012) Cross-priming for anti-tumor CTL induced by soluble Ag + polyI:C depends on the TICAM-1 pathway in mouse CD11c +/CD8α + dendritic cells. Oncoimmunology 1, 581-592
64. Ebihara, T., Shingai, M., Matsumoto, M., Wakita, T. and Seya, T. (2008) Hepatitis C virus (HCV)-infected apoptotic cells extrinsically modulate dendritic cell function to activate T cells and NK cells. Hepatology 48, 48-58
65. Lee, J., Sayed, N., Hunter, A., Au, K. F., Wong, W. H., Mocarski, E. S., Pera, R. R., Yakubov, E. and Cooke, JP. (2012) Activation of innate immunity is required for efficient nuclear reprogramming. Cell 151, 547-558
66. Fire, A., Xu, S., Montgomery, M. K., Kostas, S. A., Driver, S. E. and Mello, C. C. (1998) Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 391, 806-811
67. Baulcombe, D. (2004) RNA silencing in plants. Nature 431, 356-363
68. Wang, X. H., Aliyari, R., Li, W. X., Li, H. W., Kim, K., Carthew, R., Atkinson, P. and Ding, S. W. (2006) RNA interference directs innate immunity against viruses in adult Drosophila. Science 312, 452-454
69. Saleh, M. C., van Rij, R. P., Hekele, A., Gillis, A., Foley, E., O'Farrell, P. H. and Andino, R. (2006) The endocytic pathway mediates cell entry of dsRNA to induce RNAi silencing. Nat. Cell Biol. 8, 793-802
70. Saleh, M. C., Tassetto, M., van Rij, R. P., Goic, B., Gausson, V., Berry, B., Jacquier, C., Antoniewski, C. and Andino, R. (2009) Antiviral immunity in Drosophila requires systemic RNA interference spread. Nature 458, 346-350
71. Feinberg, E. H. and Hunter, C. P. (2003) Transport of dsRNA into cells by the transmembrane protein SID-1. Science 301, 1545-1547
72. McEwan, D. L., Weisman, A. S. and Hunter, C. P. (2012) Uptake of extracellular double-stranded RNA by SID-2. Mol. Cell 47, 746-754
73. Karikó, K., Buckstein, M., Ni, H. and Weissman, D. (2005) Suppression of RNA recognition by Toll-like receptors: the impact of nucleoside modification and the evolutionary origin of RNA. Immunity 23, 165-75
74. Kawashima, T., Kosaka, A., Yan, H., Guo, Z., Uchiyama, R., Fukui, R., Kaneko, D., Kumagai, Y., You, D. J., Carreras, J. et al. (2013) Double-stranded RNA of intestinal commensal but not pathogenic bacteria triggers production of protective interferon-β. Immunity 38, 1187-97
75. Gowen, B. B., Wong, M. H., Jung, K. H., Sanders, A. B., Mitchell, W. M., Alexopoulou, L., Flavell, R. A. and Sidwell, R. W. (2007) TLR3 is essential for the induction of protective immunity against Punta Toro Virus infection by the double-stranded RNA (dsRNA), poly(I:C12U), but not Poly(I:C): differential recognition of synthetic dsRNA molecules. J. Immunol. 178, 5200-5208