CpG DNA: Trigger of sepsis, mediator of protection, or both?

Scandinavian Journal of Infectious Diseases

Volumn 35, Issue 9, 2003, Pages 653-659

  Krieg, Arthur M ^a  

^a PFIZER INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BACTERIAL DNA; BACTERIUM LIPOPOLYSACCHARIDE; BCG VACCINE; CHEMOKINE; CLARITHROMYCIN; CYTOKINE; GENOMIC DNA; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERLEUKIN 12; OLIGODEOXYNUCLEOTIDE; PEPTIDE ANTIBODY; QS 21; REACTIVE OXYGEN METABOLITE; TOLL LIKE RECEPTOR 9; TUMOR NECROSIS FACTOR;

CPG ISLAND; CYTOKINE RELEASE; DISEASE PREDISPOSITION; DRUG POTENTIATION; GENE EXPRESSION; GENE SEQUENCE; GENETIC PREDISPOSITION; HUMAN; IMMUNE RESPONSE; IMMUNOCOMPETENT CELL; IMMUNOSTIMULATION; MOUSE; MYCOBACTERIUM AVIUM; MYCOBACTERIUM TUBERCULOSIS; NONHUMAN; REVIEW; SEPSIS; SEQUENCE ANALYSIS; SYSTEMIC INFLAMMATORY RESPONSE SYNDROME; VIRUS PARTICLE;

ADJUVANTS, IMMUNOLOGIC; ANIMALS; HUMANS; IMMUNITY, CELLULAR; MICE; MICE, INBRED BALB C; OLIGODEOXYRIBONUCLEOTIDES; SYSTEMIC INFLAMMATORY RESPONSE SYNDROME;

EID: 0242320205     PISSN: 00365548     EISSN: None     Source Type: Journal    
DOI: 10.1080/00365540310015999     Document Type: Review

References (91)

1. Janeway Jr CA, Medzhitov R. Innate immune recognition. Annu Rev Immunol 2002: 20: 197-216.
2. Krieg AM. CpG motifs in bacterial DNA and their immune effects. Annu Rev Immunol 2002; 20: 709-60.
3. Krug A, Towarowski A, Britsch S, Rothenfusser S, Hornung V, Bals R, et al. Toll-like receptor expression reveals CpG DNA as a unique microbial stimulus for plasmacytoid dendritic cells which synergizes with CD40 ligand to induce high amounts of IL-12. Eur J Immunol 2001; 31: 3026-37.
4. Kadowaki N, Ho S, Antonenko S, de Waal MR, Kastelein RA, Bazan F, Liu YJ. Subsets of human dendritic cell precursors express different toll-like receptors and respond to different microbial antigens. J Exp Med 2001; 194: 863-70.
5. Bauer S, Kirschning CJ, Hacker H, Redecke V, Hausmann S, Akira S. et al. Human TLR9 confers responsiveness to bacterial DNA via species-specific CpG motif recognition. Proc Natl Acad Sci USA 2001; 98: 9237-42.
6. Cowdery JS, Chace JH, Yi AK, Krieg AM. Bacterial DNA induces NK cells to produce IFN-γ in vivo and increases the toxicity of lipopolysaccharides. J Immunol 1996; 156: 4570-5.
7. Ballas ZK, Rasmussen WL, Krieg AM. Induction of NK activity in murine and human cells by CpG motifs in oligodeoxynucleotides and bacterial DNA. J Immunol 1996; 157: 1840-5.
8. Krug A, Rothenfusser S, Hornung V, Jahrsdorfer B, Blackwell S, Ballas ZK, et al. Identification of CpG oligonucleotide sequences with high induction of IFN-alpha/beta in plasmacytoid dendritic cells. Eur J Immunol 2001; 31: 2154-63.
9. Yamamoto M, Sato S, Hemmi H, Sanjo H, Uematsu S, Kaisho T, et al. Essential role for TIRAP in activation of the signalling cascade shared by TLR2 and TLR4. Nature 2002; 420: 324-9.
10. Horng T, Barton GM, Flavell RA, Medzhitov R. The adaptor molecule TIRAP provides signalling specificity for Toll-like receptors. Nature 2002; 420: 329-33.
11. Gao JJ, Diesl V, Wittmann T, Morrison DC, Ryan JL, Vogel SN, Follettie MT. Regulation of gene expression in mouse macrophages stimulated with bacterial CpG-DNA and lipopolysaccharide. J Leukoc Biol 2002; 72: 1234-45.
12. Hume DA, Underhill DM, Sweet MJ, Ozinsky AO, Liew FY, Aderem A. Macrophages exposed continuously to lipopolysaccharide and other agonists that act via toll-like receptors exhibit a sustained and additive activation state. BMC Immunol 2001; 2: 11.
13. Zhang H, Tay PN, Cao W, Li W, Lu J. Integrin-nucleated Toll-like receptor (TLR) dimerization reveals subcellular targeting of TLRs and distinct mechanisms of TLR4 activation and signaling. FEBS Lett 2002; 532: 171-6.
14. Cowdery JS, Boerth NJ, Norian LA, Myung PS, Koretzky GA. Differential regulation of the IL-12 p40 promoter and of p40 secretion by CpG DNA and lipopolysaccharide. J Immunol 1999: 162: 6770-5.
15. Dalpke AH, Frey M, Morath S, Hartung T, Heeg K. Interaction of lipoteichoic acid and CpG-DNA during activation of innate immune cells. Immunobiology 2002; 206: 392-407.
16. Mason N, Aliberti J, Caamano JC, Liou HC, Hunter CA. Cutting edge: identification of c-Rel-dependent and -independent pathways of IL-12 production during infectious and inflammatory stimuli. J Immunol 2002; 2590-4.
17. Bradford M, Schroeder AJ, Morse III HC, Vogel SN, Cowdery JS. CpG DNA induced IL-12 p40 gene activation is independent of STAT1 activation or production of interferon consensus sequence binding protein. J Biomed Sci 2002; 9: 688-96.
18. Myers LP, Krieg AM, Pruett SB. Bacterial DNA does not increase serum corticosterone concentration or prevent increases induced by other stimuli. Int Immunopharmacol 2001; 1: 1605-14.
19. Hartmann G, Krieg AM. CpG DNA and LPS induce distinct patterns of activation in human monocytes. Gene Ther 1999; 6: 893-903.
20. Sparwasser T, Hultner L, Koch ES, Luz A, Lipford GB, Wagner H. Immunostimulatory CpG-oligodeoxynucleotides cause extramedullary murine hemopoiesis. J Immunol 1999; 162: 2368-74.
21. Utaisincharoen P, Kespichayawattana W, Anuntagool N, Chaisuriya P, Pichyangkul S, Krieg AM, Sirisinha S. CpG ODN enhances uptake of bacteria by mouse macrophages. Clin Exp Immunol 2003; 132: 70-5.
22. Gao JJ, Xue Q, Papasian CJ, Morrison DC. Bacterial DNA and lipopolysaccharide induce synergistic production of TNF-alpha through a post-transcriptional mechanism. J Immunol 2001; 166: 6855-60.
23. Yi AK, Yoon J-G, Hong S-C, Redford T, Krieg AM. Lipopolysaccharide and CpG DNA synergize for tumor necrosis factor-α production through activation of NF-κB. Int Immunol 2001; 13: 1391-404.
24. Jin L, Raymond DP, Crabtree TD, Pelletier SJ, Rudy CK, Pruett TL, Sawyer RG. Preexposure of murine macrophages to CpG-containing oligonucleotides results in nuclear factor kappaB p50 homodimer-associated hyporesponsiveness, Surgery 2002: 245-51.
25. Yeo SJ, Yoon JG, Hong SC, Yi AK. CpG DNA induces self and cross-hyporesponsiveness of RAW264.7 cells in response to CpG DNA and lipopolysaccharide: alterations in IL-1 receptor-associated kinase expression. J Immunol 2003; 170: 1052-61.
26. An H, Yu Y, Zhang M, Xu H, Qi R, Yan X, et al. Involvement of ERK, p38 and NF-kappaB signal transduction in regulation of TLR2, TLR4 and TLR9 gene expression induced by lipopolysaccharide in mouse dendritic cells. Immunology 2002; 106: 38-45.
27. Sparwasser T, Miethke T, Lipford G, Borschert K, Hacker H, Heeg K, Wagner H. Bacterial DNA causes septic shock (Letter). Nature 1997; 386: 336-7.
28. Sparwasser T, Miethke T, Lipford G, Erdmann A, Hacker H, Heeg K, Wagner H. Macrophages sense pathogens via DNA motifs: induction of tumor necrosis factor-α-mediated shock. Eur J Immunol 1997; 27: 1671-9.
29. Cornelie S, Wiel E, Lund N, Lebuffe G, Vendeville C, Riveau G, et al. Cytosine-phosphate-guanine (CpG) motifs are sensitizing agents for lipopolysaccharide in toxic shock model. Intensive Care Med 2002; 28: 1340-7.
30. Krieg AM, Love-Homan L, Yi AK, Harty JT. CpG DNA induces sustained IL-12 expression in vivo and resistance to Listeria monocytogenes challenge. J Immunol 1998; 161: 2428-34.
31. Elkins KL, Rhinehart-Jones TR, Stibitz S, Conover JS, Klinman DM. Bacterial DNA containing CpG motifs stimulates lymphocyte-dependent protection of mice against lethal infection with intracellular bacteria. J Immunol 19ft 162: 2291-8.
32. Oxenius A, Martinic MM, Hengartner H, Klenerman P. CpG-containing oligonucleotides are efficient adjuvants for induction of protective antiviral immune responses with T-cell peptide vaccines. J Virol 1999: 73: 4120-6.
33. Klinman DM, Conover J, Coban C. Repeated administration of synthetic oligodeoxynucleotides expressing CpG motifs provides long-term protection against bacterial infection. Infect Immun 1999; 67: 5658-63.
34. Klinman DM, Kamstrup S, Verthelyi D, Gursel I, Ishii KJ, Takeshita F, Gursel M. Activation of the innate immune system by CpG oligodeoxynucleotides: immunoprotective activity and safety. Springer Semin Immunopathol 2002; 22: 173-83.
35. Freidag BL, Melton GB, Collins F, Klinman DM, Cheever A, Stobie L, et al. CpG oligodeoxynucleotides and interleukin-12 improve the efficacy of Mycobacterium bovis BCG vaccination in mice challenged with M. tuberculosis. Infect Immun 2000; 68: 2948-53.
36. Juffermans NP, Leemans JC, Florquin S, Verbon A, Kolk AH, Speelman P, et at. CpG oligodeoxynucleotides enhance host defense during murine tuberculosis. Infect Immun 2002; 70: 147-52.
37. Hayashi T, Rao SP, Takabayashi K, Van Uden JH, Kornbluth RS, Baird SM, et al. Enhancement of innate immunity against Mycobacterium avium infection by immunostimulatory DNA is mediated by indoleamine 2,3-dioxygenase. Infect Immun 2001; 69: 6156-64.
38. Lipford GB, Sparwasser T, Zimmermann S, Heeg K, Wagner H. CpG-DNA-mediated transient lymphadenopathy is associated with a state of Th1 predisposition to antigen-driven responses. J Immunol 2000; 165: 1228-35.
39. Zimmermann S, Egeter O, Hausmann S, Lipford GB, Rocken M, Wagner H, Heeg K. CpG oligodeoxynucleotides trigger protective and curative Th1 responses in lethal murine leishmaniasis. J Immunol 1998: 160: 3627-30.
40. Lipford GB, Sparwasser T, Bauer M, Zimmermann S, Koch ES, Heeg K, Wagner H. Immunostimulatory DNA: sequence-dependent production of potentially harmful or useful cytokines. Eur J Immunol 1997; 27: 3420-6.
41. Walker PS, Scharton-Kersten T, Krieg AM, Love-Homan L, Rowton ED, Udey MC, Vogel JC. Immunostimulatory oligodeoxynucleotides promote protective immunity and provide systemic therapy for leishmaniasis via IL-12- and IFN-γ-dependent mechanisms. Proc Natl Acad Sci U S A 1999; 96: 6970-5.
42. Stacey KJ, Blackwell JM. Immunostimulatory DNA as an adjuvant in vaccination against Leishmania major. Infect Immun 1999; 67: 3719-26.
43. Olbrich AR, Schimmer S, Heeg K, Schepers K, Schumacher TN, Dittmer U. Effective postexposure treatment of retrovirus-induced disease with immunostimulatory DNA containing CpG motifs. J Virol 2002; 76: 11397-404.
44. Sethi S, Lipford G, Wagner H, Kretzschmar H. Postexposure prophylaxis against prion disease with a stimulator of innate immunity. Lancet 2002; 360: 229-30.
45. Sedegah M, Finkelman F, Hoffman SL. Interleukin 12 induction of interferon γ-dependent protection against malaria. Proc Natl Acad Sci USA 1994: 91: 10700-2.
46. Gramzinski RA, Sedegah M, Doolan D, Krieg AM, Davis HL, Hoffman SL. IL12- and IFN-γ-dependent protection of mice against malaria conferred by CpG DNA. Infect Immun 2001; 69: 1643-49.
47. Klinman DM, Verthelyi D, Takeshita F, Ishii KJ. Immune recognition of foreign DNA: a cure for bioterrorism? Immunity 1999; 11: 123-9.
48. Pyles RB, Higgins D, Chalk C, Zalar A, Eiden J, Brown C, Van Nest G, Stanberry LR. Use of immunostimulatory sequence-containing oligonucleotides as topical therapy for genital herpes simplex virus type 2 infection. J Virol 2002; 76: 11387-96.
49. Harandi AM, Eriksson K, Holmgren J. A protective role of locally administered immunostimulatory CpG oligodeoxynucleotide in a mouse model of genital herpes infection. J Virol 2003; 77: 953-62.
50. Cho JY, Miller M, Back KJ, Castaneda D, Nayar J, Roman M, et al. Immunostimulatory DNA sequences inhibit respiratory syncytial viral load, airway inflammation, and mucus secretion. J Allergy Clin Immunol 2001; 108: 697-702.
51. Weighardt H, Feterowski C, Veit M, Rump M, Wagner H, Holzmann B. Increased resistance against acute polymicrobial sepsis in mice challenged with immunostimulatory CpG oligodeoxynucleotides is related to an enhanced innate effector cell response. J Immunol 2000; 165: 4537-43.
52. Gomis S, Babiuk L, Godson DL, Allan B, Thrush T, Townsend H, et al. Protection of chickens against Escherichia coli infections by DNA containing CpG motifs. Infect Immun 2003; 71: 857-63.
53. Chu RS, McCool T, Greenspan NS, Schreiber JR, Harding CV. CpG oligodeoxynucleotides act as adjuvants for pneumococcal polysaccharide-protein conjugate vaccines and enhance antipolysaccharide immunoglobulin G2a (IgG2a) and IgG3 antibodies. Infect Immun 2000: 68: 1450-6.
54. Kovarik J, Bozzotti P, Tougne C, Davis HL, Lambert PH, Krieg AM, Siegrist CA. Adjuvant effects of CpG oligodeoxynucleotides on responses against T-independent type 2 antigens. Immunology 2001; 102: 67-76.
55. von Hunolstein C, Telom R, Mariotti S, Recchia S, Orefici G, Nisini R. Synthetic oligodeoxynucleotide containing CpG motif induces an anti-polysaccharide type 1-like immune response after immunization of mice with Haemophilus influenzae type b conjugate vaccine. Int Immunol 2000; 12: 295-303.
56. Tighe H, Takabayashi K, Schwartz D, Marsden R, Beck L, Corbeil J, et al. Conjugation of protein to immunostimulatory DNA results in a rapid, long-lasting and potent induction of cell-mediated and humoral immunity. Eur J Immunol 2000; 30: 1939-47.
57. Cho HJ, Takabayashi K, Cheng PM, Nguyen MD, Corr M, Tuck S, Raz E. Immunostimulatory DNA-based vaccines induce cytotoxic lymphocyte activity by a T-helper cell-independent mechanism. Nat Biotechnol 2000; 18: 509-14.
58. Kim SK, Ragupathi G, Musselli C, Choi SJ, Park YS, Livingston PO. 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 1999; 18: 597-603.
59. Chu RS, Targoni OS, Krieg AM, Lehmann PV, Harding CV. CpG oligodeoxynucleotides act as adjuvants that switch on T helper 1 (Th1) immunity. J Exp Med 1997; 186: 1623-31.
60. Lipford GB, Bauer M, Blank C, Reiter R, Wagner H, Heeg K. CpG-containing synthetic oligonucleotides promote B and cytotoxic T cell responses to protein antigen: a new class of vaccine adjuvants. Eur J Immunol 1997; 27: 2340-4.
61. Roman M, Martin-Orozco E, Goodman JS, Nguyen MD, Sato Y, Ronaghy A, et al. Immunostimulatory DNA sequences function as T helper-1-promoting adjuvants. Nat Med 1997; 3: 849-54.
62. Davis HL. Use of CpG DNA for enhancing specific immune responses. Curr Top Microbiol Immunol 2000; 247: 171-83.
63. Kim SK, Ragupathi G, Cappello S, Kagan E, Livingston PO. Effect of immunological adjuvant combinations on the antibody and T-cell response to vaccination with MUC1-KLH and GD3-KLH conjugates. Vaccine 2000; 19: 530-7.
64. Horner AA, Ronaghy A, Cheng PM, Nguyen MD, Cho HJ, Broide D, Raz E. Immunostimulatory DNA is a potent mucosal adjuvant. Cell Immunol 1998; 190: 77-82.
65. McCluskie MJ, Davis HL. CpG DNA is a potent enhancer of systemic and mucosal immune responses against hepatitis B Surface antigen with intranasal administration to mice. J Immunol 1998; 161: 4463-6.
66. McCluskie MJ, Davis HL. Oral, intrarectal and intranasal immunizations using CpG and non-CpG oligodeoxynucleotides as adjuvants. Vaccine 2000; 19: 413-22.
67. McCluskie MJ, Weeratna RD, Clements JD, Davis HL. Mucosal immunization of mice using CpG DNA and/or mutants of the heat-labile enterotoxin of Escherichia coli as adjuvants. Vaccine 2001; 19: 3759-68.
68. McCluskie MJ, Weeratna RD, Davis HL. The potential of oligodeoxynucleotides as mucosal and parenteral adjuvants. Vaccine 2001; 19: 2657-60.
69. McCluskie MJ, Weeratna RD, Krieg AM, Davis HL. CpG DNA is an effective oral adjuvant to protein antigens in mice. Vaccine 2000; 19: 950-7.
70. Moldoveanu Z, Love-Homan L, Huang WQ, Krieg AM. CpG DNA, a novel immune enhancer for systemic and mucosal immunization with influenza virus. Vaccine 1998; 16: 1216-24.
71. Olszewska W, Partidos CD, Steward MW. Antipeptide antibody responses following intranasal immunization: effectiveness of mucosal adjuvants. Infect Immun 2000; 68: 4923-9.
72. Gierynska M, Kumaraguru U, Eo SK, Lee S, Krieg A, Rouse BT. Induction of CD8 T-cell-specific systemic and mucosal immunity against herpes simplex virus with CpG-peptide complexes. J Virol 2002; 76: 6568-76.
73. Choi AH, McNeal MM, Flint JA, Basu M, Lycke NY, Clements JD, et al. The level of protection against rotavirus shedding in mice following immunization with a chimeric VP6 protein is dependent on the route and the coadministered adjuvant. Vaccine 2002; 20: 1733-40.
74. Gallichan WS, Woolstencroft RN, Guarasci T, McCluskie MJ, Davis HL, Rosenthal KL. Intranasal immunization with CpG oligodeoxynucleotides as an adjuvant dramatically increases IgA and protection against herpes simplex virus-2 in the genital tract. J Immunol 2001; 166: 3451-7.
75. Mariotti S, Teloni R, von Hunolstein C, Romagnoli G, Orefici G, Nisini R. Immunogenicity of anti-Haemophilus influenzae type b CRM197 conjugate following mucosal vaccination with oligodeoxynucleotide containing immunostimulatory sequences as adjuvant. Vaccine 2002; 20: 2229-39.
76. McCluskie MJ, Wen YM, Di Q, Davis HL. Immunization against hepatitis B virus by mucosal administration of antigen-antibody complexes. Viral Immunol 1998; 11: 245-52.
77. Gerber S, Lane C, Brown DM, Lord E, DiLorenzo M, Clements JD, et al. Human papillomavirus virus-like particles are efficient oral immunogens when coadministered with Escherichia coli heat-labile enterotoxin mutant R192G or CpG DNA. J Virol 2001; 75: 4752-4760
78. Kang SM, Compans RW. Enhancement of mucosal immunization with virus-like particles of simian immunodeficiency virus. J Virol 2003; 77: 3615-23.
79. Joseph A, Louria-Hayon I, Plis-Finarov A, Zeira E, Zakay-Rones Z, Raz E, et al. Liposomal immunostimulatory DNA sequence (ISS-ODN): an efficient parenteral and mucosal adjuvant for influenza and hepatitis B vaccines. Vaccine 2002; 20: 3342-54.
80. Krieg AM, Yi AK, Matson S, Waldschmidt TJ, Bishop GA, Teasdale R, et al. CpG motifs in bacterial DNA trigger direct B-cell activation. Nature 1995; 374: 546-9.
81. Yi AK, Chang M, Peckham DW, Krieg AM, Ashman RF. CpG oligodeoxyribonucleotides rescue mature spleen B cells from spontaneous apoptosis and promote cell cycle entry (Published erratum appears in J Immunol 1999; 163: 1093). J Immunol 1998; 160: 5898-906.
82. Yi AK, Hornbeck P, Lafrenz DE, Krieg AM. CpG DNA rescue of murine B lymphoma cells from anti-IgM-induced growth arrest and programmed cell death is associated with increased expression of c-myc and bcl-xL. J Immunol 1996; 157: 4918-25.
83. Sparwasser T, Vabulas RM, Villmow B, Lipford GB, Wagner H. Bacterial CpG-DNA activates dendritic cells in vivo: T helper cell-independent cytotoxic T cell responses to soluble proteins. Eur J Immunol 2000; 30: 3591-7.
84. Vabulas RM, Pircher H, Lipford GB, Hacker H, Wagner H. CpG-DNA activates in vivo T cell epitope presenting dendritic cells to trigger protective antiviral cytotoxic T cell responses. J Immunol 2000; 164: 2372-8.
85. + T cell dependent. J Immunol 1999; 163: 1880-7.
86. Davis HL, Weeratna R, Waldschmidt TJ, Tygrett L, Schorr J, Krieg AM, Weeratna R. CpG DNA is a potent enhancer of specific immunity in mice immunized with recombinant hepatitis B surface antigen (Published erratum appears in J Immunol 1999; 162: 3103). J Immunol 1998; 160: 870
87. Jones TR, Obaldia III N, Gramzinski RA, Charoenvit Y, Kolodny N, Kitov S, et al. Synthetic oligodeoxynucleotides containing CpG motifs enhance immunogenicity of a peptide malaria vaccine in Aotus monkeys. Vaccine 1999; 17: 3065-71.
88. Hartmann G, Weeratna RD, Ballas ZK, Payette P, Blackwell S, Suparto I, et al. Delineation of a CpG phosphorothioate oligodeoxynucleotide for activating primate immune responses in vitro and in vivo. J Immunol 2000; 164: 1617-24.
89. Davis HL, Suparto I, Weeratna R, Juminarto ID, Chamzah S, Ma'ruf A, et al. CpG DNA overcomes hyporesponsiveness to hepatitis B vaccine in orangutans. Vaccine 2000; 18: 1920-4.
90. Krieg AM. From A to Z on CpG. Trends Immunol 2002; 23: 64-5.
91. Cooper CL, Davis H, Morris ML, Seguin I, Angel JB, Elfer SM, Cameron DW. Safe and effective use of CpG as adjuvant for HBV vaccination in HIV infection. Proceedings of Conference, Boston, MA, 2003