Therapeutic targeting of innate immunity with Toll-like receptor agonists and antagonists

Nature Medicine

Volumn 13, Issue 5, 2007, Pages 552-559

  Kanzler, Holger ^a   Barrat, Franck J ^a   Hessel, Edith M ^a   Coffman, Robert L ^a  

^a Dynavax Technologies Corporation   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1018 ISS; 852 A; ADJUVANT; AMPLIGEN; ANA 975; ANTHRAX VACCINE; AVE 0675; CPG OLIGODEOXYNUCLEOTIDE; CRX 675; E 6020; ERITORAN; HEPATITIS B VACCINE; HEPLISAV; HUMAN IMMUNODEFICIENCY VIRUS VACCINE; HYB 2093; IMIQUIMOD; IMO 2125; IMOXINE; INFLUENZA VACCINE; IPH 31XX; IRS 954; POLLINEX QUATTRO; R 850; R 851; RESIQUIMOD; SM 36032; SOTIRIMOD; STIMUVAX; TAK 242; TOLAMBA; TOLL LIKE RECEPTOR; TOLL LIKE RECEPTOR AGONIST; TOLL LIKE RECEPTOR ANTAGONIST; UNCLASSIFIED DRUG; UNINDEXED DRUG; VACCINE; VAXIMMUNE; VIRUS FUSION PROTEIN; WART VIRUS VACCINE;

ACTINIC KERATOSIS; ADAPTIVE IMMUNITY; ALLERGIC RHINITIS; ALLERGY; ANTHRAX; ANTIGEN RECOGNITION; ANTIMICROBIAL ACTIVITY; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ASTHMA; AUTOIMMUNITY; BASAL CELL CARCINOMA; BREAST CANCER; CANCER; CANCER CHEMOTHERAPY; CELLULAR IMMUNITY; CHRONIC FATIGUE SYNDROME; CLINICAL TRIAL; COLORECTAL CANCER; CONDYLOMA; CYTOTOXICITY TEST; DRUG MECHANISM; DRUG POTENCY; DRUG SYNTHESIS; DRUG TARGETING; EFFECTOR CELL; GENITAL HERPES; HEPATITIS B; HEPATITIS C; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS; IMMUNE RESPONSE; IMMUNE SYSTEM; IMMUNOREGULATION; INFLAMMATION; INFLUENZA; INNATE IMMUNITY; KIDNEY CARCINOMA; LUNG NON SMALL CELL CANCER; MELANOMA; NONHODGKIN LYMPHOMA; NONHUMAN; PRIORITY JOURNAL; REVIEW; SENSORY SYSTEM; STIMULATION; VIRUS INFECTION; WART VIRUS;

ANIMALS; ANTIGENS; AUTOIMMUNITY; HUMANS; HYPERSENSITIVITY; IMMUNITY, NATURAL; INFLAMMATION; MODELS, IMMUNOLOGICAL; NEOPLASMS; TOLL-LIKE RECEPTORS; VIRUS DISEASES;

EID: 34249677845     PISSN: 10788956     EISSN: 1546170X     Source Type: Journal    
DOI: 10.1038/nm1589     Document Type: Review

References (98)

1. Janeway, C.A. Jr. How the immune system works to protect the host from infection: a personal view. Proc. Natl. Acad. Sci. USA 98, 7461-7468 (2001).
2. Janeway, C.A. Jr. & Medzhitov, R. Innate immune recognition. Annu. Rev. Immunol. 20, 197-216 (2002).
3. Sansonetti, P.J. The innate signaling of dangers and the dangers of innate signaling. Nat. Immunol. 7, 1237-1242 (2006).
4. Meylan, E., Tschopp, J. & Karin, M. Intracellular pattern recognition receptors in the host response. Nature 442, 39-44 (2006).
5. Akira, S., Uematsu, S. & Takeuchi, O. Pathogen recognition and innate immunity. Cell 124, 783-801 (2006).
6. Hoebe, K. et al. TLR signaling pathways: opportunities for activation and blockade in pursuit of therapy. Curr. Pharm. Des. 12, 4123-4134 (2006).
7. Lemaitre, B., Nicolas, E., Michaut, L., Reichhart, J.M. & Hoffmann, J.A. The dorsoventral regulatory gene cassette spatzle/Toll/cactus controls the potent antifungal response in Drosophila adults. Cell 86, 973-983 (1996).
8. Hoffmann, J.A. The immune response of Drosophila. Nature 426, 33-38 (2003).
9. Medzhitov, R., Preston-Hulburt, P. & Janeway, C.A. A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature 388, 394-397 (1997).
10. Roach, J.C. et al. The evolution of vertebrate Toll-like receptors. Proc. Natl. Acad. Sci. USA 102, 9577-9582 (2005).
11. Rock, F.L., Hardiman, G., Timans, J.C., Kastelein, R.A. & Bazan, J.F. A family of human receptors structurally related to Drosophila Toll. Proc. Natl. Acad. Sci. USA 95, 588-593 (1998).
12. Rast, J.P., Smith, L.C., Loza-Coll, M., Hibino, T. & Litman, G.W. Genomic insights into the immune system of the sea urchin. Science 314, 952-956 (2006).
13. Choe, J., Kelker, M.S. & Wilson, I.A. Crystal structure of human toll-like receptor 3 (TLR3) ectodomain. Science 309, 581-585 (2005).
14. Bell, J.K. et al. The molecular structure of the Toll-like receptor 3 ligand-binding domain. Proc. Natl. Acad. Sci. USA 102, 10976-10980 (2005).
15. Akira, S. & Hemmi, H. Recognition of pathogen-associated molecular patterns by TLR family. Immunol. Lett. 85, 85-95 (2003).
16. Latz, E. et al. TLR9 signals after translocating from the ER to CpG DNA in the lysosome. Nat. Immunol. 5, 190-198 (2004).
17. Lee, J. et al. Maintenance of colonic homeostasis by distinctive apical TLR9 signalling in intestinal epithelial cells. Nat. Cell Biol. 8, 1327-1336 (2006).
18. Akira, S. & Takeda, K. Toll-like receptor signalling. Nat. Rev. Immunol. 4, 499-511 (2004).
19. Marshak-Rothstein, A. Toll-like receptors in systemic autoimmune disease. Nat. Rev. Immunol. 6, 823-835 (2006).
20. Hasan, U. et al. Human TLR10 is a functional receptor, expressed by B cells and plasmacytoid dendritic cells, which activates gene transcription through MyD88. J. Immunol. 174, 2942-2950 (2005).
21. Krieg, A.M. Therapeutic potential of Toll-like receptor 9 activation. Nat. Rev. Drug Discov. 5, 471-484 (2006).
22. Tomai, M.A., Miller, R.L., Lipson, K.E., Vasilakos, J.P. & Woulfe, S.L. Immune response modifiers: Imiquimod and future drugs for modulating the immune response. Drug Discov. Today Ther. Strateg. [online] 3, 342-352 (2006).
23. Lee, J. et al. Molecular basis for the immunostimulatory activity of guanine nucleoside analogs: activation of Toll-like receptor 7. Proc. Natl. Acad. Sci. USA 100, 6646-6651 (2003).
24. Evans, J.T. et al. Enhancement of antigen-specific immunity via the TLR4 ligands MPL adjuvant and Ribi.529. Expert Rev. Vaccines 2, 219-229 (2003).
25. Alexopoulou, L., Holt, A.C., Medzhitov, R. & Flavell, R.A. Recognition of double-stranded RNA and activation of NF-kappaB by Toll-like receptor 3. Nature 413, 732-738 (2001).
26. Gay, N.J., Gangloff, M. & Weber, A.N. Toll-like receptors as molecular switches. Nat. Rev. Immunol. 6, 693-698 (2006).
27. Moynagh, P.N. TLR signalling and activation of IRFs: revisiting old friends from the NF-κB pathway. Trends Immunol. 26, 469-476 (2005).
28. Stetson, D.B. & Medzhitov, R. Type I interferons in host defense. Immunity 25, 373-381 (2006).
29. Honda, K., Takaoka, A. & Taniguchi, T. Type I interferon [corrected] gene induction by the interferon regulatory factor family of transcription factors. Immunity 25, 349-360 (2006).
30. Iwasaki, A. & Medzhitov, R. Toll-like receptor control of the adaptive immune responses. Nat. Immunol. 5, 987-995 (2004).
31. Hornef, M.W. & Bogdan, C. The role of epithelial Toll-like receptor expression in host defense and microbial tolerance. J. Endotoxin Res. 11, 124-128 (2005).
32. Hayashi, F., Means, T.K. & Luster, A.D. Toll-like receptors stimulate human neutrophil function. Blood 102, 2660-2669 (2003).
33. Butcher, E.C., Williams, M., Youngman, K., Rott, L. & Briskin, M. Lymphocyte trafficking and regional immunity. Adv. Immunol. 72, 209-253 (1999).
34. Han, J. & Ulevitch, R.J. Limiting inflammatory responses during activation of innate immunity. Nat. Immunol. 6, 1198-1205 (2005).
35. Steinman, R.M. & Hemmi, H. Dendritic cells: translating innate to adaptive immunity. Curr. Top. Microbiol. Immunol. 311, 17-58 (2006).
36. Pulendran, B. & Ahmed, R. Translating innate immunity into immunological memory: implications for vaccine development. Cell 124, 849-863 (2006).
37. Banchereau, J. & Steinman, R.M. Dendritic cells and the control of immunity. Nature 392, 245-252 (1998).
38. Kawai, T. & Akira, S. Innate immune recognition of viral infection. Nat. Immunol. 7, 131-137 (2006).
39. Colonna, M., Trinchieri, G. & Liu, Y.J. Plasmacytoid dendritic cells in immunity. Nat. Immunol. 5, 1219-1226 (2004).
40. Krieg, A.M., Efler, S.M., Wittpoth, M., Al Adhami, M.J. & Davis, H.L. Induction of systemic TH1-like innate immunity in normal volunteers following subcutaneous but not intravenous administration of CPG 7909, a synthetic B-class CpG oligodeoxynucleotide TLR9 agonist. J. Immunother. 27, 460-471 (2004).
41. Rakoff-Nahoum, S., Paglino, J., Eslami-Varzaneh, F., Edberg, S. & Medzhitov, R. Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis. Cell 118, 229-241 (2004).
42. Katakura, K. et al. Toll-like receptor 9-induced type I IFN protects mice from experimental colitis. J. Clin. Invest. 115, 695-702 (2005).
43. Datta, S.K., Cho, H.J., Takabayashi, K., Horner, A.A. & Raz, E. Antigen-immunostimulatory oligonucleotide conjugates: mechanisms and applications. Immunol. Rev. 199, 217-226 (2004).
44. Dupont, J. et al. A controlled clinical trial comparing the safety and immunogenicity of a new adjuvanted hepatitis B vaccine with a standard hepatitis B vaccine. Vaccine 24, 7167-7174 (2006).
45. Halperin, S.A. et al. Comparison of the safety and immunogenicity of hepatitis B virus surface antigen co-administered with an immunostimulatory phosphorothioate oligonucleotide and a licensed hepatitis B vaccine in healthy young adults. Vaccine 24, 20-26 (2006).
46. Harper, D.M. et al. Sustained efficacy up to 4.5 years of a bivalent L1 virus-like particle vaccine against human papillomavirus types 16 and 18: follow-up from a randomised control trial. Lancet 367, 1247-1255 (2006).
47. Rock, K.L. & Shen, L. Cross-presentation: underlying mechanisms and role in immune surveillance. Immunol. Rev. 207, 166-183 (2005).
48. Hodi, F.S. & Dranoff, G. Combinatorial cancer immunotherapy. Adv. Immunol. 90, 341-368 (2006).
49. + T cell responses to vaccination with peptide, IFA, and CpG oligodeoxynucleotide 7909. J. Clin. Invest. 115, 739-746 (2005).
50. Krieg, A.M. Antitumor applications of stimulating toll-like receptor 9 with CpG oligodeoxynucleotides. Curr. Oncol. Rep. 6, 88-95 (2004).
51. Zaks, K. et al. Efficient immunization and cross-priming by vaccine adjuvants containing TLR3 or TLR9 agonists complexed to cationic liposomes. J. Immunol. 176, 7335-7345 (2006).
52. Cho, H.J. et al. Immunostimulatory DNA-based vaccines induce cytotoxic lymphocyte activity by a T-helper cell-independent mechanism. Nat. Biotechnol. 18, 509-514 (2000).
53. + T cell responses in nonhuman primates. Proc. Natl. Acad. Sci. USA 102, 15190-15194 (2005).
54. + T cell response. Immunity 25, 655-664 (2006).
55. Blander, J.M. & Medzhitov, R. On regulation of phagosome maturation and antigen presentation. Nat. Immunol. 7, 1029-1035 (2006).
56. Butts, C. et al. Randomized phase IIB trial of BLP25 liposome vaccine in stage IIIB and IV non-small-cell lung cancer. J. Clin. Oncol. 23, 6674-6681 (2005).
57. Marshall, J.D. et al. Polymyxin B enhances ISS-mediated immune responses across multiple species. Cell. Immunol. 229, 93-105 (2004).
58. Storni, T. et al. Critical role for activation of antigen-presenting cells in priming of cytotoxic T cell responses after vaccination with virus-like particles. J. Immunol. 168, 2880-2886 (2002).
59. Horner, A.A., Redecke, V. & Raz, E. Toll-like receptor ligands: hygiene, atopy and therapeutic implications. Curr. Opin. Allergy Clin. Immunol. 4, 555-561 (2004).
60. Racila, D.M. & Kline, J.N. Perspectives in asthma: molecular use of microbial products in asthma prevention and treatment. J. Allergy Clin. Immunol. 116, 1202-1205 (2005).
61. Tulic, M.K. et al. Amb a 1-immunostimulatory oligodeoxynucleotide conjugate immunotherapy decreases the nasal inflammatory response. J. Allergy Clin. Immunol. 113, 235-241 (2004).
62. Creticos, P.S. et al. Immunotherapy with a ragweed-toll-like receptor 9 agonist vaccine for allergic rhinitis. N. Engl. J. Med. 355, 1445-1455 (2006).
63. Bochner, B.S. & Busse, W.W. Allergy and asthma. J. Allergy Clin. Immunol. 115, 953-959 (2005).
64. Larche, M. Immunoregulation by targeting T cells in the treatment of allergy and asthma. Curr. Opin. Immunol. 18, 745-750 (2006).
65. Julia, V. et al. A restricted subset of dendritic cells captures airborne antigens and remains able to activate specific T cells long after antigen exposure. Immunity 16, 271-283 (2002).
66. Gauvreau, G.M. et al. Immunostimulatory sequences regulate interferon-inducible genes but not allergic airway responses. Am. J. Respir. Crit. Care Med. 174, 15-20 (2006).
67. Moisan, J. et al. TLR7 ligand prevents allergen-induced airway hyperresponsiveness and eosinophilia in allergic asthma by a MYD88-dependent and MK2-independent pathway. Am. J. Physiol. Lung Cell. Mol. Physiol. 290, L987-L995 (2006).
68. Serebrisky, D. et al. CpG oligodeoxynucleotides can reverse Th2-associated allergic airway responses and alter the B7.1/B7.2 expression in a murine model of asthma. J. Immunol. 165, 5906-5912 (2000).
69. Kline, J.N. et al. CpG oligodeoxynucleotides do not require TH1 cytokines to prevent eosinophilic airway inflammation in a murine model of asthma. J. Allergy Clin. Immunol. 104, 1258-1264 (1999).
70. Hessel, E.M. et al. Immunostimulatory oligonucleotides block allergic airway inflammation by inhibiting Th2 cell activation and IgE-mediated cytokine induction. J. Exp. Med. 202, 1563-1573 (2005).
71. Fanucchi, M.V. et al. Immunostimulatory oligonucleotides attenuate airways remodeling in allergic monkeys. Am. J. Respir. Crit. Care Med. 170, 1153-1157 (2004).
72. Coffman, R.L. & Hessel, E.M. Nonhuman primate models of asthma. J. Exp. Med. 201, 1875-1879 (2005).
73. Tayyari, F., Sutton, T.C., Manson, H.E. & Hegele, R.G. CpG-oligodeoxynucleotides inhibit RSV-enhanced allergic sensitisation in guinea pigs. Eur. Respir. J. 25, 295-302 (2005).
74. Chang, Y.C., Madkan, V., Cook-Norris, R., Sra, K. & Tyring, S. Current and potential uses of imiquimod. South. Med. J. 98, 914-920 (2005).
75. Jahrsdorfer, B. et al. Immunostimulatory oligodeoxynucleotides induce apoptosis of B cell chronic lymphocytic leukemia cells. J. Leukoc. Biol. 77, 378-387 (2005).
76. Salaun, B., Coste, I., Rissoan, M.C., Lebecque, S.J. & Renno, T. TLR3 can directly trigger apoptosis in human cancer cells. J. Immunol. 176, 4894-490 1 (2006).
77. Gekeler, V. et al. G3139 and other CpG-containing immunostimulatory phosphorothioate oligodeoxynucleotides are potent suppressors of the growth of human tumor xenografts in nude mice. Oligonucleotides 16, 83-93 (2006).
78. Fletcher, S., Steffy, K. & Averett, D. Masked oral prodrugs of toll-like receptor 7 agonists: a new approach for the treatment of infectious disease. Curr. Opin. Investig. Drugs 7, 702-708 (2006).
79. Klinman, D.M. Immunotherapeutic uses of CpG oligodeoxynucleotides. Nat. Rev. Immunol. 4, 249-258 (2004).
80. Amlie-Lefond, C. et al. Innate immunity for biodefense: a strategy whose time has come. J. Allergy Clin. Immunol. 116, 1334-1342 (2005).
81. Rossignol, D.P. & Lynn, M. TLR4 antagonists for endotoxemia and beyond. Curr. Opin. Investig. Drugs 6, 496-502 (2005).
82. Wang, T. et al. Toll-like receptor 3 mediates West Nile virus entry into the brain causing lethal encephalitis. Nat. Med. 10, 1366-1373 (2004).
83. + T cell proliferation by inducing indoleamine 2,3-dioxygenase in plasmacytoid dendritic cells. Blood 109, 3351-3359 (2007).
84. Hooks, J.J. et al. Immune interferon in the circulation of patients with autoimmune disease. N. Engl. J. Med. 301, 5-8 (1979).
85. Bennett, L. et al. Interferon and granulopoiesis signatures in systemic lupus erythematosus blood. J. Exp. Med. 197, 711-723 (2003).
86. Baechler, E.C. et al. Interferon-inducible gene expression signature in peripheral blood cells of patients with severe lupus. Proc. Natl. Acad. Sci. USA 100, 2610-2615 (2003).
87. Baccala, R., Hoebe, K., Kono, D.H., Beutler, B. & Theofilopoulos, A.N. Toll-like receptor-dependent and-independent pathways of type I interferon induction in systemic autoimmunity. Nat. Med. 13, 543-551 (2007).
88. Ronnblom, L. & Alm, G.V. Systemic lupus erythematosus and the type I interferon system. Arthritis Res. Ther. 5, 68-75 (2003).
89. Van Ghelue, M., Moens, U., Bendiksen, S. & Rekvig, O.P. Autoimmunity to nucleosomes related to viral infection: a focus on hapten-carrier complex formation. J. Autoimmun. 20, 171-182 (2003).
90. Lund, J., Sato, A., Akira, S., Medzhitov, R. & Iwasaki, A. Toll-like receptor 9-mediated recognition of Herpes simplex virus-2 by plasmacytoid dendritic cells. J. Exp. Med. 198, 513-520 (2003).
91. Diebold, S.S., Kaisho, T., Hemmi, H., Akira, S. & Reis e Sousa, C. Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA. Science 303, 1529-1531 (2004).
92. Barrat, F.J. et al. 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).
93. Means, T.K. et al. Human lupus autoantibody-DNA complexes activate DCs through cooperation of CD32 and TLR9. J. Clin. Invest. 115, 407-417 (2005).
94. Vollmer, J. et al. 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).
95. Lenert, P.S. Targeting Toll-like receptor signaling in plasmacytoid dendritic cells and autoreactive B cells as a therapy for lupus. Arthritis Res. Ther. 8, 203 (2006).
96. Barton, G.M., Kagan, J.C. & Medzhitov, R. Intracellular localization of Toll-like receptor 9 prevents recognition of self DNA but facilitates access to viral DNA. Nat. Immunol. 7, 49-56 (2006).
97. Jiang, D. et al. Regulation of lung injury and repair by Toll-like receptors and hyaluronan. Nat. Med. 11, 1173-1179 (2005).
98. Mollen, K.P. et al. Emerging paradigm: toll-like receptor 4-sentinel for the detection of tissue damage. Shock 26, 430-437 (2006).