TLR9 in health and disease

International Reviews of Immunology

Volumn 25, Issue 3-4, 2006, Pages 155-181

  Vollmer, Jörg ^a  

^a PFIZER INC   (United States)

Author keywords

CpG; Immune; Innate; ODN; TLR9

Indexed keywords

A CLASS CPG OLIGODEOXYNUCLEOTIDE; ANTIBODY; ANTINEOPLASTIC AGENT; B CLASS CPG OLIGODEOXYNUCLEOTIDE; C CLASS CPG OLIGODEOXYNUCLEOTIDE; CHLOROQUINE; CPG 10101; CPG OLIGODEOXYNUCLEOTIDE; DNA; HEPATITIS B VACCINE; IMMUNOLOGICAL ADJUVANT; IMMUNOMODULATING AGENT; LIGAND; NUCLEIC ACID; OLIGODEOXYNUCLEOTIDE DERIVATIVE; OLIGODEOXYNUCLEOTIDE PHOSPHOROTHIOATE; S CLASS OLIGODEOXYNUCLEOTIDE; TOLL LIKE RECEPTOR; TOLL LIKE RECEPTOR 9; UNCLASSIFIED DRUG;

ALLERGY; ANTIGEN RECOGNITION; ASTHMA; AUTOIMMUNE DISEASE; B LYMPHOCYTE ACTIVATION; CANCER; CANCER IMMUNOTHERAPY; CELL COMPARTMENTALIZATION; CLINICAL TRIAL; CPG ISLAND; CYTOKINE PRODUCTION; DISEASE PREDISPOSITION; DOSE RESPONSE; DRUG BLOOD LEVEL; DRUG EFFECT; DRUG MECHANISM; HEALTH; HEPATITIS B; HEPATITIS C; HOMEOSTASIS; HUMAN; IMMUNE RESPONSE; IMMUNE SYSTEM; IMMUNITY; IMMUNOMODULATION; IMMUNOREGULATION; IMMUNOSTIMULATION; IMMUNOSUPPRESSIVE TREATMENT; INFECTION; INNATE IMMUNITY; LIGAND BINDING; LUPUS ERYTHEMATOSUS; MOLECULAR RECOGNITION; NONHUMAN; PATHOGENICITY; PATHOLOGY; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN MOTIF; REGULATORY MECHANISM; REGULATORY T LYMPHOCYTE; REVIEW; RHEUMATOID ARTHRITIS; SIGNAL TRANSDUCTION; SINGLE NUCLEOTIDE POLYMORPHISM; SPECIES COMPARISON; TUMOR; VIRUS INFECTION;

ANIMALS; AUTOIMMUNE DISEASES; CLINICAL TRIALS; CPG ISLANDS; HUMANS; IMMUNITY; IMMUNITY, NATURAL; OLIGONUCLEOTIDES; POLYMORPHISM, SINGLE NUCLEOTIDE; T-LYMPHOCYTES; TOLL-LIKE RECEPTOR 9;

EID: 33745820869     PISSN: 08830185     EISSN: 15635244     Source Type: Journal    
DOI: 10.1080/08830180600743107     Document Type: Review

References (177)

1. P. Cristofaro and S.M. Opal, Role of toll-like receptors in infection and immunity: clinical implications, Drugs, 66: 15-29, 2006.
2. A.M. Krieg, CpG motifs: the active ingredient in bacterial extracts? Nat. Med., 9: 831-835, 2003.
3. F. Heil, H. Hemmi, H. Hochrein, F. Ampenberger, C. Kirschning, S. Akira, G. Lipford, H. Wagner, and S. Bauer, Species-specific recognition of single-stranded RNA via toll-like receptor 7 and 8, Science, 303: 1526-1529, 2004.
4. S.S. Diebold, T. Kaisho, H. Hemmi, S. Akira, and Reis e Sousa, Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA, Science, 303: 1529-1531, 2004.
5. H. Hemmi, O. Takeuchi, T. Kawai, T. Kaisho, S. Sato, H. Sanjo, M. Matsumoto, K. Hoshino, H. Wagner, K. Takeda, and S. Akira, A toll-like receptor recognizes bacterial DNA, Nature, 408: 740-745, 2000.
6. S. Sun, C. Beard, R. Jaenisch, P. Jones, and J. Sprent, Mitogenicity of DNA from different organisms for murine B cells, J. Immunol., 159: 3119-3125, 1997.
7. A.M. Krieg, A.K. Yi, S. Matson, T.J. Waldschmidt, G.A. Bishop, R. Teasdale, G.A. Koretzky, and D.M. Klinman, CpG motifs in bacterial DNA trigger direct B-cell activation, Nature, 374: 546-549, 1995.
8. J. Lund, A. Sato, S. Akira, R. Medzhitov, and A. Iwasaki, Toll-like receptor 9-mediated recognition of Herpes simplex virus-2 by plasmacytoid dendritic cells, J. Exp. Med., 198: 513-520, 2003.
9. A. Krug, G.D. Luker, W. Barchet, D.A. Leib, S. Akira, and M. Colonna, Herpes simplex virus type 1 activates murine natural interferon-producing cells through toll-like receptor 9, Blood, 103: 1433-1437, 2004.
10. A. Krug, A.R. French, W. Barchet, J.A. Fischer, A. Dzionek, J.T. Pingel, M.M. Orihuela, S. Akira, W.M. Yokoyama, and M. Colonna, TLR9-dependent recognition of MCMV by IPC and DC generates coordinated cytokine responses that activate antiviral NK cell function, Immunity, 21: 107-119, 2004.
11. K.J. Stacey, G.R. Young, F. Clark, D.P. Sester, T.L. Roberts, S. Naik, M.J. Sweet, and D.A. Hume, The molecular basis for the lack of immunostimulatory activity of vertebrate DNA, J. Immunol., 170: 3614-3620, 2003.
12. A.M. Krieg, CpG motifs in bacterial DNA and their immune effects, Annu. Rev. Immunol., 20: 709-760, 2002.
13. Z.K. Ballas, W.L. Rasmussen, and A.M. Krieg, Induction of NK activity in murine and human cells by CpG motifs in oligodeoxynucleotides and bacterial DNA, J. Immunol., 157: 1840-1845, 1996.
14. D.S. Pisetsky and C.F. Reich, III: The influence of base sequence on the immunological properties of defined oligonucleotides, Immunopharmacology, 40: 199-208, 1998.
15. G. Hartmann and A.M. Krieg, Mechanism and function of a newly identified CpG DNA motif in human primary B cells, J. Immunol., 164: 944-953, 2000.
16. G. Hartmann, R.D. Weeratna, Z.K. Ballas, P. Payette, S. Blackwell, I. Suparto, W.L. Rasmussen, M. Waldschmidt, D. Sajuthi, R.H. Purcell, H.L. Davis, and A.M. Krieg, Delineation of a CpG phosphorothioate oligodeoxynucleotide for activating primate immune responses in vitro and in vivo, J. Immunol., 164: 1617-1624, 2000.
17. D.P. Sester, S. Naik, S.J. Beasley, D.A. Hume, and K.J. Stacey, Phosphorothioate backbone modification modulates macrophage activation by CpG DNA, J. Immunol., 165: 4165-4173, 2000.
18. S. Bauer, C.J. Kirschning, H. Hacker, V. Redecke, S. Hausmann, S. Akira, H. Wagner, and G.B. Lipford, Human TLR9 confers responsiveness to bacterial DNA via species-specific CpG motif recognition, Proc. Natl. Acad. Sci. U.S.A., 98: 9237-9242, 2001.
19. J. Vollmer, R. Weeratna, P. Payette, M. Jurk, C. Schetter, M. Laucht, T. Wader, S. Tluk, M. Liu, H.L. Davis, and A.M. Krieg, Characterization of three CpG oligodeoxynucleotide classes with distinct immunostimulatory activities, Eur. J. Immunol., 34: 251-262, 2004.
20. V. Hornung, S. Rothenfusser, S. Britsch, A. Krug, B. Jahrsdorfer, T. Giese, S. Endres, and G. Hartmann, 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., 168: 4531-4537, 2002.
21. N. Kadowaki, S. Ho, S. Antonenko, R.W. Malefyt, R.A. Kastelein, F. Bazan, and Y.J. Liu, Subsets of human dendritic cell precursors express different toll-like receptors and respond to different microbial antigens, J. Exp. Med., 194: 863-869, 2001.
22. A. Krug, S. Rothenfusser, V. Hornung, B. Jahrsdorfer, S. Blackwell, Z.K. Ballas, S. Endres, A.M. Krieg, and G. Hartmann, Identification of CpG oligonucleotide sequences with high induction of IFN-alpha/beta in plasmacytoid dendritic cells, Eur. J. Immunol., 31: 2154-2163, 2001.
23. M. Kerkmann, L.T. Costa, C. Richter, S. Rothenfusser, J. Battiany, V. Hornung, J. Johnson, S. Englert, T. Ketterer, W. Heckl, S. Thalhammer, S. Endres, and G. Hartmann, Spontaneous formation of nucleic acid-based nanoparticles is responsible for high interferon-alpha induction by CpG-A in plasmacytoid dendritic cells, J. Biol. Chem., 280: 8086-8093, 2005.
24. D. Verthelyi, K.J. Ishii, M. Gursel, F. Takeshita, and D.M. Klinman, Human peripheral blood cells differentially recognize and respond to two distinct CPG motifs, J. Immunol., 166: 2372-2377, 2001.
25. J.D. Marshall, K. Fearon, C. Abbate, S. Subramanian, P. Yee, J. Gregorio, R.L. Coffman, and G. Van Nest, Identification of a novel CpG DNA class and motif that optimally stimulate B cell and plasmacytoid dendritic cell functions, J. Leukoc. Biol., 73: 781-792, 2003.
26. N. Teleshova, J. Kenney, J. Jones, J. Marshall, G. Van Nest, J. Dufour, R. Bohm, J.D. Lifson, A. Gettie, and M. Pope, CpG-C immunostimulatory oligodeoxyribonucleotide activation of plasmacytoid dendritic cells in rhesus macaques to augment the activation of IFN-gamma-secreting simian immunodeficiency virus-specific T cells, J. Immunol., 173: 1647-1657, 2004.
27. M. Jurk, B. Schulte, A. Kritzler, B. Noll, E. Uhlmann, T. Wader, C. Schetter, A.M. Krieg, and J. Vollmer, C-Class CpG ODN: sequence requirements and characterization of immunostimulatory activities on mRNA level, Immunobiology, 209: 141-154, 2004.
28. G. Hartmann, J. Battiany, H. Poeck, M. Wagner, M. Kerkmann, N. Lubenow, S. Rothenfusser, and S. Endres, Rational design of new CpG oligonucleotides that combine B cell activation with high IFN-A induction in plasmacytoid dendritic cells, Eur. J. Immunol., 33: 1633-1641, 2003.
29. W. Chu, X. Gong, Z. Li, K. Takabayashi, H. Ouyang, Y. Chen, A. Lois, D.J. Chen, G.C. Li, M. Karin, and E. Raz, DNA-PKcs is required for activation of innate immunity by immunostimulatory DNA, Cell, 103: 909-918, 2000.
30. K.J. Ishii, F. Takeshita, I. Gursel, M. Gursel, J. Conover, A. Nussenzweig, and D.M. Klinman, Potential role of phosphatidylinositol 3 kinase, rather than DNA-dependent protein kinase, in CpG DNA-induced immune activation, J. Exp. Med., 196: 269-274, 2002.
31. A.M. Dragoi, X. Fu, S. Ivanov, P. Zhang, L. Sheng, D. Wu, G.C. Li, and W.M. Chu, DNA-PKcs, but not TLR9, is required for activation of Akt by CpG-DNA, EMBO J., 24: 779-789, 2005.
32. M.J. Lehmann and G. Sczakiel, Spontaneous uptake of biologically active recombinant DNA by mammalian cells via a selected DNA segment, Gene Ther., 12: 446-451, 2005.
33. Z. Zhang, T. Weinschenk, and H.J. Schluesener, Uptake, cellular distribution and novel cellular binding proteins of immunostimulatory CpG oligodeoxynucleotides in glioblastoma cells, Mol. Cell Biochem., 272: 35-46, 2005.
34. H. Liang, C.F. Reich, D.S. Pisetsky, and P.E. Lipsky, The role of cell surface receptors in the activation of human B cells by phosphorothioate oligonucleotides, J. Immunol., 165: 1438-1445, 2000.
35. H. Liang, C.F. Reich, D.S. Pisetsky, and P.E. Lipsky, The role of surface ig binding in the activation of human B cells by phosphorothioate oligodeoxynucleotides, Scand. J. Immunol., 54: 551-563, 2001.
36. L. Peiser, S. Mukhopadhyay, and S. Gordon, Scavenger receptors in innate immunity, Curr. Opin. Immunol., 14: 123-128, 2002.
37. F.G. Zhu, C.F. Reich, and D.S. Pisetsky, The role of the macrophage scavenger receptor in immune stimulation by bacterial DNA and synthetic oligonucleotides, Immunology, 103: 226-234, 2001.
38. P. Ahmad-Nejad, H. Hacker, M. Rutz, S. Bauer, R.M. Vabulas, and H. Wagner, Bacterial CpG-DNA and lipopolysaccharides activate Toll-like receptors at distinct cellular compartments, Eur. J. Immunol., 32: 1958-1968, 2002.
39. E. Latz, A. Schoenemeyer, A. Visintin, K.A. Fitzgerald, B.G. Monks, C.F. Knetter, E. Lien, N.J. Nilsen, T. Espevik, and D.T. Golenbock, TLR9 signals after translocating from the ER to CpG DNA in the lysosome, Nat. Immunol., 5: 190-198, 2004.
40. H. Hacker, H. Mischak, T. Miethke, S. Liptay, R. Schmid, T. Sparwasser, K. Heeg, G.B. Lipford, and H. Wagner, CpG-DNA-specific activation of antigen-presenting cells requires stress kinase activity and is preceded by non-specific endocytosis and endosomal maturation, EMBO J., 17: 6230-6240, 1998.
41. D.E. Macfarlane and L. Manzel, Antagonism of immunostimulatory CpG-oligodeoxynucleotides by quinacrine, chloroquine, and structurally related compounds, J. Immunol., 160: 1122-1131, 1998.
42. A.K. Yi and A.M. Krieg, Rapid induction of mitogen-activated protein kinases by immune stimulatory CpG DNA, J. Immunol., 161: 4493-4497, 1998.
43. M. Rutz, J. Metzger, T. Gellert, P. Luppa, G.B. Lipford, H. Wagner, and S. Bauer, Toll-like receptor 9 binds single-stranded CpG-DNA in a sequence- and pH-dependent manner, Eur. J. Immunol., 34: 2541-2550, 2004.
44. S. Cornelie, J. Hoebeke, A.M. Schacht, B. Bertin, J. Vicogne, M. Capron, and G. Riveau, Direct evidence that toll-like receptor 9 (TLR9) functionally binds plasmid DNA by specific CpG motifs recognition, J. Biol. Chem., 279: 15124-15129, 2004.
45. J.K. Bell, I. Botos, P.R. Hall, J. Askins, J. Shiloach, D.M. Segal, and D.R. Davies, The molecular structure of the Toll-like receptor 3 ligand-binding domain, Proc. Natl. Acad. Sci. U. S. A., 102: 10976-10980, 2005.
46. J. Choe, M.S. Kelker, and I.A. Wilson, Crystal structure of human toll-like receptor 3 (TLR3) ectodomain, Science, 309: 581-585, 2005.
47. J.K. Bell, G.E. Mullen, C.A. Leifer, A. Mazzoni, D.R. Davies, and D.M. Segal, Leucine-rich repeats and pathogen recognition in Toll-like receptors, Trends Immunol., 24: 528-533, 2003.
48. H. Zhang, P.N. Tay, W. Cao, W. Li, and J. Lu, Integrin-nucleated Toll-like receptor (TLR) dimerization reveals subcellular targeting of TLRs and distinct mechanisms of TLR4 activation and signaling, FEBS Lett., 532: 171-176, 2002.
49. T. Nishiya and A.L. DeFranco, Ligand-regulated chimeric receptor approach reveals distinctive subcellular localization and signaling properties of the Toll-like receptors, J. Biol. Chem., 279: 19008-19017, 2004.
50. G.M. Barton and R. Medzhitov, Toll-like receptor signaling pathways, Science, 300: 1524-1525, 2003.
51. S. Uematsu, S. Sato, M. Yamamoto, T. Hirotani, H. Kato, F. Takeshita, M. Matsuda, C. Coban, K.J. Ishii, T. Kawai, O. Takeuchi, and S. Akira, Interleukin-1 receptor-associated kinase-1 plays an essential role for Toll-like receptor (TLR)7- and TLR9-mediated interferon-{alpha} induction, J. Exp. Med., 201: 915-923, 2005.
52. H. Xu, H. An, Y. Yu, M. Zhang, R. Qi, and X. Cao, Ras participates in CpG oligodeoxynucleotide signaling through association with toll-like receptor 9 and promotion of interleukin-1 receptor-associated kinase/tumor necrosis factor receptor-associated factor 6 complex formation in macrophages, J. Biol. Chem., 278: 36334-36340, 2003.
53. H. Tsujimura, T. Tamura, H.J. Kong, A. Nishiyama, K.J. Ishii, D.M. Klinman, and K. Ozato, Toll-like receptor 9 signaling activates NF-kappaB through IFN regulatory factor-8/IFN consensus sequence binding protein in dendritic cells, J. Immunol., 172: 6820-6827, 2004.
54. K. Yang, A. Puel, S. Zhang, C. Eidenschenk, C.L. Ku, A. Casrouge, C. Picard, H. von Bernuth, B. Senechal, S. Plancoulaine, S. Al Hajjar, A. Al Ghonaium, L. Marodi, D. Davidson, D. Speert, C. Roifman, B.Z. Garty, A. Ozinsky, F.J. Barrat, R.L. Coffman, R.L. Miller, X. Li, P. Lebon, C. Rodriguez-Gallego, H. Chapel, F. Geissmann, E. Jouanguy, and J.L. Casanova, Human TLR-7-, -8-, and -9-mediated induction of IFN-alpha/beta and -lambda Is IRAK-4 dependent and redundant for protective immunity to viruses, Immunity, 23: 465-478, 2005.
55. P. Tailor, T. Tamura, and K. Ozato, IRF family proteins and type I interferon induction in dendritic cells, Cell Res., 16: 134-140, 2006.
56. C. Schetter and J. Vollmer, Toll-like receptors involved in the response to microbial pathogens: Development of agonists for toll-like receptor 9, Curr. Opin. Drug Discov. Dev., 7: 204-210, 2004.
57. F. Takeshita and D.M. Klinman, CpG ODN-mediated regulation of IL-12 p40 transcription, Eur. J. Immunol., 30: 1967-1976, 2000.
58. A.K. Yi, J.G. Yoon, S.J. Yeo, S.C. Hong, B.K. English, and A.M. Krieg, Role of mitogen-activated protein kinases in CpG DNA-mediated IL-10 and IL-12 production: central role of extracellular signal-regulated kinase in the negative feedback loop of the CpG DNA-mediated Th1 response, J. Immunol., 168: 4711-4720, 2002.
59. A.K. Yi, J.G. Yoon, and A.M. Krieg, Convergence of CpG DNA- and BCR-mediated signals at the c-Jun N-terminal kinase and NF-kappaB activation pathways: regulation by mitogen-activated protein kinases, Int. Immunol., 15: 577-591, 2003.
60. M. Schnare, A.C. Holt, K. Takeda, S. Akira, and R. Medzhitov, Recognition of CpG DNA is mediated by signaling pathways dependent on the adaptor protein MyD88, Curr. Biol., 10: 1139-1142, 2000.
61. R. Takauji, S. Iho, H. Takatsuka, S. Yamamoto, T. Takahashi, H. Kitagawa, H. Iwasaki, R. Iida, T. Yokochi, and T. Matsuki, CpG-DNA-induced IFN-alpha production involves p38 MAPK-dependent STAT1 phosphorylation in human plasmacytoid dendritic cell precursors, J. Leukoc. Biol., 72: 1011-1019, 2002.
62. M. Muzio, G. Natoli, S. Saccani, M. Levrero, and A. Mantovani, The human toll signaling pathway: divergence of nuclear factor kappaB and JNK/SAPK activation upstream of tumor necrosis factor receptor-associated factor 6 (TRAF6). J. Exp. Med., 187: 2097-2101, 1998.
63. H. Hacker, R.M. Vabulas, O. Takeuchi, K. Hoshino, S. Akira, and H. Wagner, Immune cell activation by bacterial CpG-DNA through myeloid differentiation marker 88 and tumor necrosis factor receptor-associated factor (TRAF6), J. Exp. Med., 192: 595-600, 2000.
64. T. Kawai, S. Sato, K.J. Ishii, C. Coban, H. Hemmi, M. Yamamoto, K. Terai, M. Matsuda, J.I. Inoue, S. Uematsu, O. Takeuchi, and S. Akira, Interferon-alpha induction through Toll-like receptors involves a direct interaction of IRF7 with MyD88 and TRAF6, Nat. Immunol., 5: 1061-1068, 2004.
65. K. Honda, H. Yanai, T. Mizutani, H. Negishi, N. Shimada, N. Suzuki, Y. Ohba, A. Takaoka, W.C. Yeh, and T. Taniguchi, Role of a transductional- transcriptional processor complex involving MyD88 and IRF-7 in Toll-like receptor signaling, Proc. Natl. Acad. Sci. U. S. A., 101: 15416-15421, 2004.
66. K. Honda, H. Yanai, A. Takaoka, and T. Taniguchi, Regulation of the type I IFN induction: a current view, Int. Immunol., 17: 1367-1378, 2005.
67. S.J. Yeo, D. Gravis, J.G. Yoon, and A.K. Yi, Myeloid differentiation factor 88-dependent transcriptional regulation of cyclooxygenase-2 expression by CpG DNA: role of NF-kappaB and p38, J. Biol. Chem., 278: 22563-22573, 2003.
68. D.K. Ghosh, M.A. Misukonis, C. Reich, D.S. Pisetsky, and J.B. Weinberg, Host response to infection: the role of CpG DNA in induction of cyclooxygenase 2 and nitric oxide synthase 2 in murine macrophages, Infect. Immun., 69: 7703-7710, 2001.
69. Y. Chen, J. Zhang, S.A. Moore, Z.K. Ballas, J.P. Portanova, A.M. Krieg, and D.J. Berg, CpG DNA induces cyclooxygenase-2 expression and prostaglandin production, Int. Immunol., 13: 1013-1020, 2001.
70. B. Bohle, L. Orel, D. Kraft, and C. Ebner, Oligodeoxynucleotides containing CpG motifs induce low levels of TNF-alpha in human B lymphocytes: possible adjuvants for Th1 responses, J. Immunol., 166: 3743-3748, 2001.
71. O. Duramad, K.L. Fearon, J.H. Chan, H. Kanzler, J.D. Marshall, R.L. Coffman, and F.J. Barrat, IL-10 regulates plasmacytoid dendritic cell response to CpG containing immunostimulatory sequences, Blood, 102: 4487-4492, 2003.
72. H. Gary-Gouy, P. Lebon, and A.H. Dalloul, Type I interferon production by plasmacytoid dendritic cells and monocytes is triggered by viruses, but the level of production is controlled by distinct cytokines, J. Interferon Cytokine Res., 22: 653-659, 2002.
73. A.P. Vicari, C. Chiodoni, C. Vaure, S. Ait-Yahia, C. Dercamp, F. Matsos, O. Reynard, C. Taverne, P. Merle, M.P. Colombo, A. O'Garra, G. Trinchieri, and C. Caux, Reversal of tumor-induced dendritic cell paralysis by CpG immunostimulatory oligonucleotide and anti-interleukin 10 receptor antibody, J. Exp. Med., 196: 541-549, 2002.
74. C. Dercamp, K. Chemin, C. Caux, G. Trinchieri, and A.P. Vicari, Distinct and overlapping roles of interleukin-10 and CD25+ regulatory T cells in the inhibition of antitumor CD8 T-cell responses, Cancer Res., 65: 8479-8486, 2005.
75. M. Martin, K. Rehani, R.S. Jope, and S.M. Michalek, Toll-like receptor-mediated cytokine production is differentially regulated by glycogen synthase kinase 3, Nat. Immunol., 6: 777-784, 2005.
76. K.W. Moore, M.R. de Waal, R.L. Coffman, and A. O'Garra, Interleukin-10 and the interleukin-10 receptor, Annu. Rev. Immunol., 19: 683-765, 2001.
77. F.N. Lauw, D. Pajkrt, C.E. Hack, M. Kurimoto, S.J. van Deventer, and P.T. van der, Proinflammatory effects of IL-10 during human endotoxemia, J. Immunol., 165: 2783-2789, 2000.
78. B. Bussolati, C. Rollino, F. Mariano, F. Quarello, and G. Camussi, IL-10 stimulates production of platelet-activating factor by monocytes of patients with active systemic lupus erythematosus (SLE), Clin. Exp. Immunol., 122: 471-476, 2000.
79. M.N. Sharif, I. Tassiulas, Y. Hu, I. Mecklenbrauker, A. Tarakhovsky, and L.B. Ivashkiv, IFN-alpha priming results in a gain of proinflammatory function by IL-10: implications for systemic lupus erythematosus pathogenesis, J. Immunol., 172: 6476-6481, 2004.
80. N. Liu, N. Ohnishi, L. Ni, S. Akira, and K.B. Bacon, CpG directly induces T-bet expression and inhibits IgG1 and IgE switching in B cells, Nat. Immunol., 4: 687-693, 2003.
81. G. Lugo-Villarino, S. Ito, D.M. Klinman, and L.H. Glimcher, The adjuvant activity of CpG DNA requires T-bet expression in dendritic cells, Proc. Natl. Acad. Sci. U. S. A., 102: 13248-13253, 2005.
82. K. Kobayashi, L.D. Hernandez, J.E. Galan, C.A. Janeway, Jr., R. Medzhitov, and R.A. Flavell, IRAK-M is a negative regulator of Toll-like receptor signaling, Cell, 110: 191-202, 2002.
83. S. Gisselbrecht, The CIS/SOCS proteins: a family of cytokine-inducible regulators of signaling, Eur. Cytokine Netw., 10: 463-470, 1999.
84. A.H. Dalpke, S. Opper, S. Zimmermann, and K. Heeg, Suppressors of cytokine signaling (SOCS)-1 and SOCS-3 are induced by CpG-DNA and modulate cytokine responses in APCs, J. Immunol., 166: 7082-7089, 2001.
85. A. Mansell, R. Smith, S.L. Doyle, P. Gray, J.E. Fenner, P.J. Crack, S.E. Nicholson, D.J. Hilton, L.A. O'Neill, and P.J. Hertzog, Suppressor of cytokine signaling 1 negatively regulates Toll-like receptor signaling by mediating Mal degradation, Nat. Immunol., 7: 148-155, 2006.
86. A. Baetz, M. Frey, K. Heeg, and A.H. Dalpke, Suppressor of cytokine signaling (SOCS) proteins indirectly regulate toll-like receptor signaling in innate immune cells, J. Biol. Chem., 279: 54708-54715, 2004.
87. K.V. Salojin, I.B. Owusu, K.A. Millerchip, M. Potter, K.A. Platt, and T. Oravecz, Essential role of MAPK phosphatase-1 in the negative control of innate immune responses, J. Immunol., 176: 1899-1907, 2006.
88. K. Honda, Y. Ohba, H. Yanai, H. Negishi, T. Mizutani, A. Takaoka, C. Taya, and T. Taniguchi, Spatiotemporal regulation of MyD88-IRF-7 signalling for robust type-I interferon induction, Nature, 434: 1035-1040, 2005.
89. N.W. Schroder and R.R. Schumann, Single nucleotide polymorphisms of Toll-like receptors and susceptibility to infectious disease, Lancet Infect. Dis., 5: 156-164, 2005.
90. N.C. Arbour, E. Lorenz, B.C. Schutte, J. Zabner, J.N. Kline, M. Jones, K. Frees, J.L. Watt, and D.A. Schwartz, TLR4 mutations are associated with endotoxin hyporesponsiveness in humans, Nat. Genet., 25: 187-191, 2000.
91. R. Lazarus, W.T. Klimecki, B.A. Raby, D. Vercelli, L.J. Palmer, D.J. Kwiatkowski, E.K. Silverman, F. Martinez, and S.T. Weiss, Single-nucleotide polymorphisms in the Toll-like receptor 9 gene (TLR9): frequencies, pairwise linkage disequilibrium, and haplotypes in three U.S. ethnic groups and exploratory case-control disease association studies (small star, filled), Genomics, 81: 85-91, 2003.
92. E. Noguchi, F. Nishimura, H. Fukai, J. Kim, K. Ichikawa, M. Shibasaki, and T. Arinami, An association study of asthma and total serum immunoglobin E levels for Toll-like receptor polymorphisms in a Japanese population, Clin. Exp. Allergy, 34: 177-183, 2004.
93. B. Berghofer, T. Frommer, I.R. Konig, A. Ziegler, T.G Chakraborty, G. Bein, and H. Hackstein, Common human Toll-like receptor 9 polymorphisms and haplotypes: association with atopy and functional relevance, Clin. Exp. Allergy, 35: 1147-1154, 2005.
94. H.P. Torok, J. Glas, L. Tonenchi, G. Bruennler, M. Folwaczny, and C. Folwaczny, Crohn's disease is associated with a toll-like receptor-9 polymorphism, Gastroenterology, 127: 365-366, 2004.
95. K.M. Lammers, S. Ouburg, S.A. Morre, J.B. Crusius, P. Gionchett, F. Rizzello, C. Morselli, E. Caramelli, R. Conte, G. Poggioli, M. Campieri, and A.S. Pena, Combined carriership of TLR9-1237C and CD14-260T alleles enhances the risk of developing chronic relapsing pouchitis, World J. Gastroenterol., 11: 7323-7329, 2005.
96. S. Rakoff-Nahoum, J. Paglino, F. Eslami-Varzaneh, S. Edberg, and R. Medzhitov, Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis, Cell, 118: 229-241, 2004.
97. K. Kikuchi, Z.X. Lian, Y. Kimura, C. Selmi, G.X. Yang, S.C. Gordon, P. Invernizzi, M. Podda, R.L. Coppel, A.A. Ansari, S. Ikehara, H. Miyakawa, and M.E. Gershwin, Genetic polymorphisms of toll-like receptor 9 influence the immune response to CpG and contribute to hyper-IgM in primary biliary cirrhosis, J. Autoimmun. 24: 347-352, 2005.
98. E. Uhlmann and J. Vollmer, Recent advances in the development of immunostimulatory oligonucleotides, Curr. Opin. Drug Discov. Dev., 6: 204-217, 2003.
99. J. Vollmer, R.D. Weeratna, M. Jurk, H.L. Davis, C. Schetter, M. Wullner, T. Wader, M. Liu, A. Kritzler, and A.M. Krieg, Impact of modifications of heterocyclic bases in CpG dinucleotides on their immune-modulatory activity, J. Leukoc. Biol., 76: 1-9, 2004.
100. J. Vollmer, J.S. Jepsen, E. Uhlmann, C. Schetter, M. Jurk, T. Wader, M. Wullner, and A.M. Krieg, Modulation of CpG oligodeoxynucleotide-mediated immune stimulation by locked nucleic acid (LNA), Oligonucleotides, 14: 23-31, 2004.
101. E.R. Kandimalla, L. Bhagat, Y. Li, D. Yu, D. Wang, Y.P. Cong, S.S. Song, J.X. Tang, T. Sullivan, and S. Agrawal, Immunomodulatory oligonucleotides containing a cytosine-phosphate-2′-deoxy-7-deazaguanosine motif as potent Toll-like receptor 9 agonists, Proc. Natl. Acad. Sci. U. S. A., 102: 6925-6930, 2005.
102. E.R. Kandimalla, D. Yu, Q. Zhao, and S. Agrawal, Effect of chemical modifications of cytosine and guanine in a CpG-motif of oligonucleotides: structure-immunostimulatory activity relationships, Bioorg. Med. Chem., 9: 807-813, 2001.
103. M.J. McCluskie and H.L. Davis, Oral, intrarectal and intranasal immunizations using CpG and non-CpG oligodeoxynucleotides as adjuvants, Vaccine, 19: 413-422, 2000.
104. J. Vollmer, A. Janosch, M. Laucht, Z.K. Ballas, C. Schetter, and A.M. Krieg, Highly immunostimulatory CpG-free oligodeoxynucleotides for activation of human leukocytes, Antisense Nucleic Acid Drug Dev., 12: 165-175, 2002.
105. F. Elias, J. Flo, R.A. Lobez, J. Zorzopulos, A. Montaner, and J.M. Rodriguez, Strong CpG independent immunostimulation in humans and other primates by synthetic oligodeoxynucleotides with PyNTTTTGT motifs, J. Immunol., 22: 1-12, 2003.
106. K. Sano, H. Shirota, T. Terui, T. Hattori, and G. Tamura, Oligodeoxynucleotides without CpG motifs work as adjuvant for the induction of th2 differentiation in a sequence-independent manner, J. Immunol., 170: 2367-2373, 2003.
107. F. Elias, J. Flo, R.A. Lopez, J. Zorzopulos, A. Montaner, and J.M. Rodriguez, Strong cytosine-guanosine-independent immunostimulation in humans and other primates by synthetic oligodeoxynucleotides with PyNTTTTGT motifs, J. Immunol., 171: 3697-3704, 2003.
108. J. Vollmer, R.D. Weeratna, M. Jurk, U. Samulowitz, M.J. McCluskie, P. Payette, H.L. Davis, C. Schetter, and A.M. Krieg, Oligodeoxynucleotides lacking CpG dinucleotides mediate Toll-like receptor 9 dependent T helper type 2 biased immune stimulation, Immunology, 113: 212-223, 2004.
109. M.M. Zatz, J. Oliver, C. Samuels, A.B. Skotnicki, M.B. Sztein, and A.L. Goldstein, Thymosin increases production of T-cell growth factor by normal human peripheral blood lymphocytes, Proc. Natl. Acad. Sci. U. S. A., 81: 2882-2885, 1984.
110. M.B. Sztein, S.A. Serrate, and A.L. Goldstein, Modulation of interleukin 2 receptor expression on normal human lymphocytes by thymic hormones, Proc. Natl. Acad. Sci. U. S. A., 83: 6107-6111, 1986.
111. K.M. Malinda, G.S. Sidhu, K.K. Banaudha, J.P. Gaddipati, R.K. Maheshwari, A.L. Goldstein, and H.K. Kleinman, Thymosin alpha 1 stimulates endothelial cell migration, angiogenesis, and wound healing, J. Immunol., 160: 1001-1006, 1998.
112. L. Romani, F. Bistoni, R. Gaziano, S. Bozza, C. Montagnoli, K. Perruccio, L. Pitzurra, S. Bellocchio, A. Velardi, G. Rasi, P. Di Franceso, and E. Garaci, Thymosin {alpha} 1 activates dendritic cells for antifungal Th1 resistance through toll-like receptor signaling, Blood, 103: 4232-4239, 2004.
113. K. Adachi, H. Tsutsui, S. Kashiwamura, E. Seki, H. Nakano, O. Takeuchi, K. Takeda, K. Okumura, L. Van Kaer, H. Okamura, S. Akira, and K. Nakanishi, Plasmodium berghei infection in mice induces liver injury by an IL-12- and toll-like receptor/myeloid differentiation factor 88-dependent mechanism, J. Immunol., 167: 5928-5934, 2001.
114. S. Pichyangkul, K. Yongvanitchit, U. Kum-arb, H. Hemmi, S. Akira, A.M. Krieg, D.G. Heppner, V.A. Stewart, H. Hasegawa, S. Looareesuwan, G.D. Shanks, and R.S. Miller, Malaria blood stage parasites activate human plasmacytoid dendritic cells and murine dendritic cells through a Toll-like receptor 9-dependent pathway, J. Immunol., 172: 4926-4933, 2004.
115. P. Arese and E. Schwarzer, Malarial pigment (haemozoin): a very active 'inert' substance, Ann. Trop. Med. Parasitol., 91: 501-516, 1997.
116. C. Coban, K.J. Ishii, T. Kawai, H. Hemmi, S. Sato, S. Uematsu, M. Yamamoto, O. Takeuchi, S. Itagaki, N. Kumar, T. Horii, and S. Akira, Toll-like receptor 9 mediates innate immune activation by the malaria pigment hemozoin, J. Exp. Med., 201: 19-25, 2005.
117. F.G. Zhu, C.F. Reich, and D.S. Pisetsky, Effect of cytofectins on the immune response of murine macrophages to mammalian DNA, Immunology, 109: 255-262, 2003.
118. W. Jiang, C.F. Reich III, and D.S. Pisetsky, Mechanisms of activation of the RAW264.7 macrophage cell line by transfected mammalian DNA, Cell Immunol., 229: 31-40, 2004.
119. K. Yasuda, P. Yu, C.J. Kirschning, B. Schlatter, F. Schmitz, A. Heit, S. Bauer, H. Hochrein, and H. Wagner, Endosomal translocation of vertebrate DNA activates dendritic cells via TLR9-dependent and -independent pathways, J. Immunol., 174: 6129-6136, 2005.
120. K. Yasuda, M. Rutz, B. Schlatter, J. Metzger, P.B. Luppa, F. Schmitz, T. Haas, A. Heit, S. Bauer, and H. Wagner, CpG motif-independent activation of TLR9 upon endosomal translocation of "natural" phosphodiester DNA, Eur. J. Immunol., 36: 431-436, 2006.
121. G.M. Barton, J.C. Kagan, and R. Medzhitov, Intracellular localization of Toll-like receptor 9 prevents recognition of self DNA but facilitates access to viral DNA, Nat. Immunol., 7: 49-56, 2006.
122. K.J. Ishii, C. Coban, H. Kato, K. Takahashi, Y. Torii, F. Takeshita, H. Ludwig, G. Sutter, K. Suzuki, H. Hemmi, S. Sato, M. Yamamoto, S. Uematsu, T. Kawai, O. Takeuchi, and S. Akira, A Toll-like receptor-independent antiviral response induced by double-stranded B-form DNA, Nat. Immunol., 7: 40-48, 2005.
123. J.A. Hardin and T. Mimori, Autoantibodies to ribonucleoproteins, Clin. Rheum. Dis., 11: 485-505, 1985.
124. L. Ronnblom, M.L. Eloranta, and G.V. Alm, Role of natural interferon-alpha producing cells (plasmacytoid dendritic cells) in autoimmunity, Autoimmunity, 36: 463-472, 2003.
125. J.A. Hardin, Directing autoimmunity to nucleoprotein particles: the impact of dendritic cells and interferon alpha in lupus, J. Exp. Med., 197: 681-685, 2003.
126. S. Koutouzov, A.L. Jeronimo, H. Campos, and Z. Amoura, Nucleosomes in the pathogenesis of systemic lupus erythematosus. Rheum. Dis. Clin. North Am., 30: 529-558, ix, 2004.
127. P.M. Rumore and C.R. Steinman, Endogenous circulating DNA in systemic lupus erythematosus. Occurrence as multimeric complexes bound to histone, J. Clin. Invest., 86: 69-74, 1990.
128. Z. Amoura, J.C. Piette, H. Chabre, P. Cacoub, T. Papo, B. Wechsler, J.F. Bach, and S. Koutouzov, Circulating plasma levels of nucleosomes in patients with systemic lupus erythematosus: correlation with serum antinucleosome antibody titers and absence of clear association with disease activity, Arthritis Rheum., 40: 2217-2225, 1997.
129. M. Herrmann, R.E. Voll, O.M. Zoller, M. Hagenhofer, B.B. Ponner, and J.R. Kalden, Impaired phagocytosis of apoptotic cell material by monocyte-derived macrophages from patients with systemic lupus erythematosus, Arthritis Rheum., 41: 1241-1250, 1998.
130. E.A. Leadbetter, I.R. Rifkin, A.M. Hohlbaum, B.C. Beaudette, M.J. Shlomchik, and A. Marshak-Rothstein, Chromatin-IgG complexes activate B cells by dual engagement of IgM and Toll-like receptors, Nature, 416: 603-607, 2002.
131. M.W. Boule, C. Broughton, F. Mackay, S. Akira, A. Marshak-Rothstein, and I.R. Rifkin, Toll-like receptor 9-dependent and -independent dendritic cell activation by chromatin-immunoglobulin G complexes, J. Exp. Med., 199: 1631-1640, 2004.
132. S.R. Christensen, M. Kashgarian, L. Alexopoulou, R.A. Flavell, S. Akira, and M.J. Shlomchik, Toll-like receptor 9 controls anti-DNA autoantibody production in murine lupus, J. Exp. Med., 202: 321-331, 2005.
133. T.K. Means, E. Latz, F. Hayashi, M.R. Murali, D.T. Golenbock, and A.D. Luster, Human lupus autoantibody-DNA complexes activate DCs through cooperation of CD32 and TLR9, J. Clin. Invest., 115: 407-417, 2005.
134. C. Kambach, S. Walke, and K. Nagai, Structure and assembly of the spliceosomal small nuclear ribonucleoprotein particles, Curr. Opin. Struct. Biol., 9: 222-230, 1999.
135. J. Vollmer, S. Tluk, C. Schmitz, S. Hamm, M. Jurk, A. Forsbach, S. Akira, K.M. Kelly, W.H. Reeves, S. Bauer, and A.M. Krieg, Immune stimulation mediated by autoantigen binding sites within small nuclear RNAs involves Toll-like receptors 7 and 8, J. Exp. Med., 202: 1575-1585, 2005.
136. D.A. Martin and K.B. Elkon, Autoantibodies make a U-turn: the toll hypothesis for autoantibody specificity, J. Exp. Med., 202: 1465-1469, 2005.
137. E. Savarese, O.W. Chae, S. Trowitzsch, G. Weber, B. Kastner, S. Akira, H. Wagner, R.M. Schmid, S. Bauer, and A. Krug, U1 small nuclear ribonucleoprotein immune complexes induce type I interferon in plasmacytoid dendritic cells via TLR7, Blood, 107: 3229-3234, 2006.
138. C.M. Lau, C. Broughton, A.S. Tabor, S. Akira, R.A. Flavell, M.J. Mamula, S.R. Christensen, M.J. Shlomchik, G.A. Viglianti, I.R. Rifkin, and A. Marshak-Rothstein, RNA-associated autoantigens activate B cells by combined B cell antigen receptor/Toll-like receptor 7 engagement, J. Exp. Med., 202: 1171-1177, 2005.
139. P. Lenert, L. Stunz, A.K. Yi, A.M. Krieg, and R.F. Ashman, CpG stimulation of primary mouse B cells is blocked by inhibitory oligodeoxyribonucleotides at a site proximal to NF-kappaB activation, Antisense Nucleic Acid Drug Dev., 11: 247-256, 2001.
140. L.L. Stunz, P. Lenert, D. Peckham, A.K. Yi, S. Haxhinasto, M. Chang, A.M. Krieg, and R.F. Ashman, Inhibitory oligonucleotides specifically block effects of stimulatory CpG oligonucleotides in B cells, Eur. J. Immunol., 32: 1212-1222, 2002.
141. P. Lenert, W. Rasmussen, R.F. Ashman, and Z.K. Ballas, Structural characterization of the inhibitory DNA motif for the type A (D)-CpG-induced cytokine secretion and NK-cell lytic activity in mouse spleen cells, DNA Cell Biol., 22: 621-631, 2003.
142. P.P. Ho, P. Fontoura, P.J. Ruiz, L. Steinman, and H. Garren, An immunomodulatory GpG oligonucleotide for the treatment of autoimmunity via the innate and adaptive immune systems, J. Immunol., 171: 4920-4926, 2003.
143. I. Gursel, M. Gursel, H. Yamada, K.J. Ishii, F. Takeshita, and D.M. Klinman, Repetitive elements in mammalian telomeres suppress bacterial DNA-induced immune activation, J. Immunol., 171: 1393-1400, 2003.
144. M. Jurk, A. Kritzler, B. Schulte, E. Uhlmann, C. Schetter, A.M. Krieg, and J. Vollmer, Selective inhibition of TLR-mediated signalling by inhibitory ODN, Clin. Invest. Med., 27: 2333, 2004.
145. O. Duramad, K.L. Fearon, B. Chang, J.H. Chan, J. Gregorio, R.L. Coffman, and F.J. Barrat, Inhibitors of TLR-9 act on multiple cell subsets in mouse and man in vitro and prevent death in vivo from systemic inflammation, J. Immunol., 174: 5193-5200, 2005.
146. F.J. Barrat, T. Meeker, J. Gregorio, J.H. Chan, S. Uematsu, S. Akira, B. Chang, O. Duramad, and R.L. Coffman, Nucleic acids of mammalian origin can act as endogenous ligands for Toll-like receptors and may promote systemic lupus erythematosus, J. Exp. Med., 202: 1131-1139, 2005.
147. R.F. Ashman, J.A. Goeken, J. Drahos, and P. Lenert, Sequence requirements for oligodeoxyribonucleotide inhibitory activity, Int. Immunol., 17: 411-420, 2005.
148. L. Dong, S. Ito, K.J. Ishii, and D.M. Klinman, Suppressive oligodeoxynucleotides delay the onset of glomerulonephritis and prolong survival in lupus-prone NZB x NZW mice, Arthritis Rheum., 52: 651-658, 2005.
149. L. Dong, S. Ito, K.J. Ishii, and D.M. Klinman, Suppressive oligonucleotides protect against collagen-induced arthritis in mice, Arthritis Rheum., 50: 1686-1689, 2004.
150. S. Sakaguchi, Naturally arising CD4+ regulatory t cells for immunologic self-tolerance and negative control of immune responses, Annu. Rev. Immunol., 22: 531-562, 2004.
151. J.A. Bluestone and A.K. Abbas, Natural versus adaptive regulatory T cells, Nat. Rev. Immunol., 3: 253-257, 2003.
152. S. Sakaguchi, Naturally arising FoxpS-expressing CD25+CD4+ regulatory T cells in immunological tolerance to self and non-self, Nat. Immunol., 6: 345-352, 2005.
153. Y. Yang, C.T. Huang, X. Huang, and D.M. Pardoll, Persistent Toll-like receptor signals are required for reversal of regulatory T cell-mediated CD8 tolerance, Nat. Immunol., 5: 508-515, 2004.
154. C. Pasare and R. Medzhitov, Toll pathway-dependent blockade of CD4+CD25+ T cell-mediated suppression by dendritic cells, Science, 299: 1033-1036, 2003.
155. S. Yamazaki, T. Iyoda, K. Tarbell, K. Olson, K. Velinzon, K. Inaba, and R.M. Steinman, Direct expansion of functional CD25+CD4+ regulatory T cells by antigen-processing dendritic cells, J. Exp. Med., 198: 235-247, 2003.
156. T. Kubo, R.D. Hatton, J. Oliver, X. Liu, C.O. Elson, and C.T. Weaver, Regulatory T cell suppression and energy are differentially regulated by proinflammatory cytokines produced by TLR-activated dendritic cells, J. Immunol., 173: 7249-7258, 2004.
157. R.P. Sutmuller, M.H. den Brok, M. Kramer, E.J. Bennink, L.W. Toonen, B.J. Kullberg, L.A. Joosten, S. Akira, M.G. Netea, and G.J. Adema, Toll-like receptor 2 controls expansion and function of regulatory T cells, J. Clin. Invest., 116: 485-494, 2006.
158. I. Caramalho, T. Lopes-Carvalho, D. Ostler, S. Zelenay, M. Haury, and J. Demengeot, Regulatory T cells selectively express toll-like receptors and are activated by lipopolysaccharide, J. Exp. Med., 197: 403-411, 2003.
159. G. Peng, Z. Guo, Y. Kiniwa, K.S. Voo, W. Peng, T. Fu, D.Y. Wang, Y. Li, H.Y. Wang, and R.F. Wang, Toll-like receptor 8-mediated reversal of CD4+ regulatory T cell function, Science, 309: 1380-1384, 2005.
160. E.A. Moseman, X. Liang, A.J. Dawson, A. Panoskaltsis-Mortari, A.M. Krieg, Y.J. Liu, B.R. Blazar, and W. Chen, Human plasmacytoid dendritic cells activated by CpG oligodeoxynucleotides induce the generation of CD4+CD25+ regulatory T cells, J. Immunol., 173: 4433-4442, 2004.
161. D.M. Klinman, Use of CpG oligodeoxynucleotides as immunoprotective agents, Expert. Opin. Biol. Ther., 4: 937-946, 2004.
162. I. Hussain and J.N. Kline, CpG oligodeoxynucleotides: a novel therapeutic approach for atopic disorders, Curr. Drug Targets Inflamm. Allergy, 2: 199-205, 2003.
163. A.M. Krieg, Antitumor applications of stimulating toll-like receptor 9 with CpG oligodeoxynucleotides, Curr. Oncol. Rep., 6: 88-95, 2004.
164. C.A. Siegrist, M. Pihlgren, C. Tougne, S.M. Efler, M.L. Morris, M.J. Al Adhami, D.W. Cameron, C.L. Cooper, J. Heathcote, H.L. Davis, and P.H. Lambert, Co-administration of CpG oligonucleotides enhances the late affinity maturation process of human anti-hepatitis B vaccine response, Vaccine, 23: 615-622, 2004.
165. C.L. Cooper, H.L. Davis, J.B. Angel, M.L. Morris, S.M. Elfer, I. Seguin, A.M. Krieg, and D.W. Cameron, CPG 7909 adjuvant improves hepatitis B virus vaccine seroprotection in antiretroviral-treated HIV-infected adults, AIDS, 19: 1473-1479, 2005.
166. C.L. Cooper, H.L. Davis, M.L. Morris, S.M. Efler, A.M. Krieg, Y. Li, C. Laframboise, M.J. Al Adhami, Y. Khaliq, I. Seguin, and D.W. Cameron, Safety and immunogenicity of CPG 7909 injection as an adjuvant to Fluarix influenza vaccine, Vaccine, 22: 3136-3143, 2004.
167. S.A. Halperin, G. Van Nest, B. Smith, S. Abtahi, H. Whiley, and J.J. Eiden, A phase I study of the safety and immunogenicity of recombinant hepatitis B surface antigen co-administered with an immunostimulatory phosphorothioate oligonucleotide adjuvant, Vaccine, 21: 2461-2467, 2003.
168. C.L. Cooper, H.L. Davis, M.L. Morris, S.M. Efler, M.A. Adhami, A.M. Krieg, D.W. Cameron, and J. Heathcote, CPG 7909, an immunostimulatory TLR9 agonist oligodeoxynucleotide, as adjuvant to Engerix-B((R)) HBV vaccine in healthy adults: a double-bund phase I/II study, J. Clin. Immunol., 24: 693-701, 2004.
169. S.K. Kim, G. Ragupathi, C. Musselli, S.J. Choi, Y.S. Park, and P.O. Livingston, Comparison of the effect of different immunological adjuvants on the antibody and T-cell response to immunization with MUC1-KLH and GD3-KLH conjugate cancer vaccines, Vaccine, 18: 597-603, 1999.
170. R.D. Weeratna, S.R. Makinen, M.J. McCluskie, and H.L. Davis, TLR agonists as vaccine adjuvants: comparison of CpG ODN and Resiquimod (R-848), Vaccine, 23: 5263-5270, 2005.
171. D.E. Speiser, D. Lienard, N. Rufer, V. Rubio-Godoy, D. Rimoldi, F. Lejeune, A.M. Krieg, J.C. Cerottini, and P. Romero, Rapid and strong human CD8(+) T cell responses to accination with peptide, IFA, and CpG oligodeoxynucleotide 7909, J. Clin. Invest, 115: 739-746, 2005.
172. J. Vollmer, Progress in drug development of immunostimulatory CpG oligodeoxynucleotide ligands for TLR9, Expert. Opin. Biol. Ther., 5: 673-682, 2005.
173. R.S. Longman, A.H. Talal, I.M. Jacobson, C.M. Rice, and M.L. Albert, Normal functional capacity in circulating myeloid and plasmacytoid dendritic cells in patients with chronic hepatitis C, J. Infect. Dis., 192: 497-503, 2005.
174. D. Piccioli, S. Tavarini, S. Nuti, P. Colombatto, M. Brunetto, F. Bonino, P. Ciccorossi, F. Zorat, G. Pozzato, C. Comar, S. Abrignani, and A. Wack, Comparable functions of plasmacytoid and monocyte-derived dendritic cells in chronic hepatitis C patients and healthy donors, J. Hepatol., 42: 61-67, 2005.
175. D.D. Anthony, N.L. Yonkers, A.B. Post, R. Asaad, F.P. Heinzel, M.M. Lederman, P.V. Lehmann, and H. Valdez, Selective impairments in dendritic cell-associated function distinguish hepatitis C virus and HIV infection, J. Immunol., 172: 4907-4916, 2004.
176. T. Schmalbach, S. Efler, M.L. Morris, M. Al-Adhami, C. Laframboise, H.L. Davis, and P. Leese, CpG 10101 (Actilon) oligodeoxynucleotide TLR9 agonist: pharmacokinetics and pharmacodynamics in normal volunteers, 44th Interscience Conference on Antimicrobial Agents and Chemotherapy Abstracts, pp. 463-464, 2004.
177. J.G. McHutchinson, B.R. Bacon, S.C. Gordon, E. Lawitz, M. Shiffman, N.H. Afdhal, I.M. Jacobson, A. Muir, S.M. Efler, A.P. Vicari, K. Myette, N.K. Ahluwalia, P.P. Murzenok, G. Lipford, T.K. Schmalbach, A.M. Krieg, and H.L. Davis, Immunophenotyping profile of CPG 10101 (ActilonTM), a new TLR9 agonist antiviral for Hepatitis C, Hepatology, 42: 539A, 2005.