|
|
||||||||
CUTTING EDGE |


Departments of
*
Medicine,
Pathology, and
Preventive Medicine, University of Iowa College of Medicine, Iowa City, IA 52242 and
§
the Veterans Affairs Medical Center, Iowa City, IA 52246.
Asthma has been increasing in industrialized countries. Evidence suggests that asthma is caused by a Th2 immune response to inhaled environmental Ags and that childhood infections protect against this. We have shown that bacterial DNA contains motifs, centered on unmethylated CpG dinucleotides, which induce Th1-type responses. We hypothesized that the Th1 effect of these CpG motifs may oppose the Th2 type allergic response and suggest that this may account for the protective effect of childhood infection against asthma. We examined the effects of CpG-motif oligodeoxynucleotides (CpG ODN) in a murine model of asthma. Airway eosinophilia, Th2 cytokine induction, IgE production, and bronchial hyperreactivity were prevented by coadministration of CpG ODN with the Ag. Significantly, in a previously sensitized mouse, CpG ODN can prevent allergen-induced airway inflammation. These studies suggest that exposure to CpG DNA may protect against asthma.
This article has been cited by other articles:
![]() |
O. Tliba, Y. Amrani, and R. A. Panettieri Jr Is Airway Smooth Muscle the "Missing Link" Modulating Airway Inflammation in Asthma? Chest, January 1, 2008; 133(1): 236 - 242. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. W. J. Schroder and M. Arditi IEIIS Meeting minireview: The role of innate immunity in the pathogenesis of asthma: evidence for the involvement of Toll-like receptor signaling Innate Immunity, October 1, 2007; 13(5): 305 - 312. [Abstract] [PDF] |
||||
![]() |
U. Bhan, N. W. Lukacs, J. J. Osterholzer, M. W. Newstead, X. Zeng, T. A. Moore, T. R. McMillan, A. M. Krieg, S. Akira, and T. J. Standiford TLR9 Is Required for Protective Innate Immunity in Gram-Negative Bacterial Pneumonia: Role of Dendritic Cells J. Immunol., September 15, 2007; 179(6): 3937 - 3946. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. N. Kline Eat Dirt: CpG DNA and Immunomodulation of Asthma Proceedings of the ATS, July 1, 2007; 4(3): 283 - 288. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. Camateros, M. Tamaoka, M. Hassan, R. Marino, J. Moisan, D. Marion, M.-C. Guiot, J. G. Martin, and D. Radzioch Chronic Asthma-induced Airway Remodeling Is Prevented by Toll-like Receptor-7/8 Ligand S28463 Am. J. Respir. Crit. Care Med., June 15, 2007; 175(12): 1241 - 1249. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. R. Flores, K. A. Diggs, L. M. Tait, and P. A. Morel IFN-{gamma} Negatively Regulates CpG-Induced IL-10 in Bone Marrow-Derived Dendritic Cells J. Immunol., January 1, 2007; 178(1): 211 - 218. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Inoue and Y. Aramaki Suppression of Skin Lesions by Transdermal Application of CpG-Oligodeoxynucleotides in NC/Nga Mice, a Model of Human Atopic Dermatitis J. Immunol., January 1, 2007; 178(1): 584 - 591. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. M. Gauvreau, E. M. Hessel, L.-P. Boulet, R. L. Coffman, and P. M. O'Byrne Immunostimulatory Sequences Regulate Interferon-inducible Genes but not Allergic Airway Responses Am. J. Respir. Crit. Care Med., July 1, 2006; 174(1): 15 - 20. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Moisan, P. Camateros, T. Thuraisingam, D. Marion, H. Koohsari, P. Martin, M. L. Boghdady, A. Ding, M. Gaestel, M. C. Guiot, 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, May 1, 2006; 290(5): L987 - L995. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Bergeron and L.-P. Boulet Structural changes in airway diseases: characteristics, mechanisms, consequences, and pharmacologic modulation. Chest, April 1, 2006; 129(4): 1068 - 1087. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. S. Leino, H. T. Alenius, N. Fyhrquist-Vanni, H. J. Wolff, K. E. Reijula, E.-L. Hintikka, M. S. Salkinoja-Salonen, T. Haahtela, and M. J. Makela Intranasal Exposure to Stachybotrys chartarum Enhances Airway Inflammation in Allergic Mice Am. J. Respir. Crit. Care Med., March 1, 2006; 173(5): 512 - 518. [Abstract] [Full Text] [PDF] |
||||
![]() |
E. M. Hessel, M. Chu, J. O. Lizcano, B. Chang, N. Herman, S. A. Kell, M. Wills-Karp, and R. L. Coffman Immunostimulatory oligonucleotides block allergic airway inflammation by inhibiting Th2 cell activation and IgE-mediated cytokine induction J. Exp. Med., December 5, 2005; 202(11): 1563 - 1573. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Zhang-Hoover, P. Finn, and J. Stein-Streilein Modulation of Ovalbumin-Induced Airway Inflammation and Hyperreactivity by Tolerogenic APC J. Immunol., December 1, 2005; 175(11): 7117 - 7124. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. E. NIEUWENHUIZEN and A. L. LOPATA Fighting Food Allergy: Current Approaches Ann. N.Y. Acad. Sci., November 1, 2005; 1056(1): 30 - 45. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Fedulov, E. Silverman, Y. Xiang, A. Leme, and L. Kobzik Immunostimulatory CpG Oligonucleotides Abrogate Allergic Susceptibility in a Murine Model of Maternal Asthma Transmission J. Immunol., October 1, 2005; 175(7): 4292 - 4300. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. Weigt, C. Nassenstein, T. Tschernig, P. F. Muhlradt, N. Krug, and A. Braun Efficacy of Macrophage-activating Lipopeptide-2 Combined with Interferon-{gamma} in a Murine Asthma Model Am. J. Respir. Crit. Care Med., September 1, 2005; 172(5): 566 - 572. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. R. Gordon, F. Li, A. Nayyar, J. Xiang, and X. Zhang CD8{alpha}+, but Not CD8{alpha}-, Dendritic Cells Tolerize Th2 Responses via Contact-Dependent and -Independent Mechanisms, and Reverse Airway Hyperresponsiveness, Th2, and Eosinophil Responses in a Mouse Model of Asthma J. Immunol., August 1, 2005; 175(3): 1516 - 1522. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Patel, D. Xu, P. Kewin, B. Choo-Kang, C. McSharry, N. C. Thomson, and F. Y. Liew TLR2 Agonist Ameliorates Established Allergic Airway Inflammation by Promoting Th1 Response and Not via Regulatory T Cells J. Immunol., June 15, 2005; 174(12): 7558 - 7563. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. J. Youn, M. Miller, K. J. Baek, J. W. Han, J. Nayar, S. Y. Lee, K. McElwain, S. McElwain, E. Raz, and D. H. Broide Immunostimulatory DNA Reverses Established Allergen-Induced Airway Remodeling J. Immunol., December 15, 2004; 173(12): 7556 - 7564. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. C. Deng, T. A. Moore, M. W. Newstead, X. Zeng, A. M. Krieg, and T. J. Standiford CpG Oligodeoxynucleotides Stimulate Protective Innate Immunity against Pulmonary Klebsiella Infection J. Immunol., October 15, 2004; 173(8): 5148 - 5155. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. Banerjee, K. J. Kelly, J. N. Fink, J. D. Henderson Jr., N. K. Bansal, and V. P. Kurup Modulation of Airway Inflammation by Immunostimulatory CpG Oligodeoxynucleotides in a Murine Model of Allergic Aspergillosis Infect. Immun., October 1, 2004; 72(10): 6087 - 6094. [Abstract] [Full Text] [PDF] |
||||
![]() |
I. Hussain, V. V. Jain, P. O'Shaughnessy, T. R. Businga, and J. Kline Effect of Nitrogen Dioxide Exposure on Allergic Asthma in a Murine Model Chest, July 1, 2004; 126(1): 198 - 204. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Y. Cho, M. Miller, K. J. Baek, J. W. Han, J. Nayar, M. Rodriguez, S. Y. Lee, K. McElwain, S. McElwain, E. Raz, et al. Immunostimulatory DNA Inhibits Transforming Growth Factor-{beta} Expression and Airway Remodeling Am. J. Respir. Cell Mol. Biol., May 1, 2004; 30(5): 651 - 661. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. K. Ikeda, M. Miller, J. Nayar, L. Walker, J. Y. Cho, K. McElwain, S. McElwain, E. Raz, and D. H. Broide Accumulation of Peribronchial Mast Cells in a Mouse Model of Ovalbumin Allergen Induced Chronic Airway Inflammation: Modulation by Immunostimulatory DNA Sequences J. Immunol., November 1, 2003; 171(9): 4860 - 4867. [Abstract] [Full Text] [PDF] |
||||
![]() |
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., November 1, 2003; 171(9): 4920 - 4926. [Abstract] [Full Text] [PDF] |
||||
![]() |
V. V. Jain, T. R. Businga, K. Kitagaki, C. L. George, P. T. O'Shaughnessy, and J. N. Kline Mucosal immunotherapy with CpG oligodeoxynucleotides reverses a murine model of chronic asthma induced by repeated antigen exposure Am J Physiol Lung Cell Mol Physiol, November 1, 2003; 285(5): L1137 - L1146. [Abstract] [Full Text] [PDF] |
||||
![]() |
D.-J. Chiang, Y.-L. Ye, W.-L. Chen, Y.-L. Lee, N.-Y. Hsu, and B.-L. Chiang Ribavirin or CpG DNA Sequence-Modulated Dendritic Cells Decrease the IgE Level and Airway Inflammation Am. J. Respir. Crit. Care Med., September 1, 2003; 168(5): 575 - 580. [Abstract] [Full Text] [PDF] |
||||
![]() |
E. S. Silverman and J. M. Drazen Immunostimulatory DNA for Asthma: Better than Eating Dirt Am. J. Respir. Cell Mol. Biol., June 1, 2003; 28(6): 645 - 647. [Full Text] [PDF] |
||||
![]() |
R. K. Ikeda, J. Nayar, J. Y. Cho, M. Miller, M. Rodriguez, E. Raz, and D. H. Broide Resolution of Airway Inflammation following Ovalbumin Inhalation: Comparison of ISS DNA and Corticosteroids Am. J. Respir. Cell Mol. Biol., June 1, 2003; 28(6): 655 - 663. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Nowak-Wegrzyn Future Approaches to Food Allergy Pediatrics, June 1, 2003; 111(6): 1672 - 1680. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y. Wang and A. M. Krieg Synergy between CpG- or non-CpG DNA and specific antigen for B cell activation Int. Immunol., February 1, 2003; 15(2): 223 - 231. [Abstract] [Full Text] [PDF] |
||||
![]() |
H.-J. Anders, B. Banas, Y. Linde, L. Weller, C. D. Cohen, M. Kretzler, S. Martin, V. Vielhauer, D. Schlondorff, and H.-J. Grone Bacterial CpG-DNA Aggravates Immune Complex Glomerulonephritis: Role of TLR9-Mediated Expression of Chemokines and Chemokine Receptors J. Am. Soc. Nephrol., February 1, 2003; 14(2): 317 - 326. [Abstract] [Full Text] [PDF] |
||||
![]() |
W. Jiang, H. J. Baker, and B. F. Smith Mucosal Immunization with Helicobacter, CpG DNA, and Cholera Toxin Is Protective Infect. Immun., January 1, 2003; 71(1): 40 - 46. [Abstract] [Full Text] [PDF] |
||||
![]() |
T.-Y. Kim, H.-J. Myoung, J.-H. Kim, I.-S. Moon, T.-G. Kim, W.-S. Ahn, and J.-I. Sin Both E7 and CpG-Oligodeoxynucleotide Are Required for Protective Immunity against Challenge with Human Papillomavirus 16 (E6/E7) Immortalized Tumor Cells: Involvement of CD4+ and CD8+ T Cells in Protection Cancer Res., December 15, 2002; 62(24): 7234 - 7240. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. K. Choudhury, J. S. Wild, R. Alam, D. M. Klinman, I. Boldogh, N. Dharajiya, W. J. Mileski, and S. Sur In Vivo Role of p38 Mitogen-Activated Protein Kinase in Mediating the Anti-inflammatory Effects of CpG Oligodeoxynucleotide in Murine Asthma J. Immunol., November 15, 2002; 169(10): 5955 - 5961. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. Kitagaki, V. V. Jain, T. R. Businga, I. Hussain, and J. N. Kline Immunomodulatory Effects of CpG Oligodeoxynucleotides on Established Th2 Responses Clin. Vaccine Immunol., November 1, 2002; 9(6): 1260 - 1269. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y.-H. Rha, C. Taube, A. Haczku, A. Joetham, K. Takeda, C. Duez, M. Siegel, M. K. Aydintug, W. K. Born, A. Dakhama, et al. Effect of Microbial Heat Shock Proteins on Airway Inflammation and Hyperresponsiveness J. Immunol., November 1, 2002; 169(9): 5300 - 5307. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. N. Kline, K. Kitagaki, T. R. Businga, and V. V. Jain Treatment of established asthma in a murine model using CpG oligodeoxynucleotides Am J Physiol Lung Cell Mol Physiol, July 1, 2002; 283(1): L170 - L179. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Gursel, D. Verthelyi, I. Gursel, K. J. Ishii, and D. M. Klinman Differential and competitive activation of human immune cells by distinct classes of CpG oligodeoxynucleotide J. Leukoc. Biol., May 1, 2002; 71(5): 813 - 820. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. Nau and H. Eiffert Modulation of Release of Proinflammatory Bacterial Compounds by Antibacterials: Potential Impact on Course of Inflammation and Outcome in Sepsis and Meningitis Clin. Microbiol. Rev., January 1, 2002; 15(1): 95 - 110. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. Renz and U. Herz The bidirectional capacity of bacterial antigens to modulate allergy and asthma Eur. Respir. J., January 1, 2002; 19(1): 158 - 171. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Plaut Immune-Based, Targeted Therapy for Allergic Diseases JAMA, December 19, 2001; 286(23): 3005 - 3006. [Full Text] [PDF] |
||||
![]() |
Z. K. Ballas, A. M. Krieg, T. Warren, W. Rasmussen, H. L. Davis, M. Waldschmidt, and G. J. Weiner Divergent Therapeutic and Immunologic Effects of Oligodeoxynucleotides with Distinct CpG Motifs J. Immunol., November 1, 2001; 167(9): 4878 - 4886. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y. Shibata, I. Honda, J. P. Justice, M. R. Van Scott, R. M. Nakamura, and Q. N. Myrvik Th1 Adjuvant N-Acetyl-D-Glucosamine Polymer Up-Regulates Th1 Immunity but Down-Regulates Th2 Immunity against a Mycobacterial Protein (MPB-59) in Interleukin-10-Knockout and Wild-Type Mice Infect. Immun., October 1, 2001; 69(10): 6123 - 6130. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Hertz, S. Mahalingam, I. Dalum, S. Klysner, J. Mattes, A. Neisig, S. Mouritsen, P. S. Foster, and A. Gautam Active Vaccination Against IL-5 Bypasses Immunological Tolerance and Ameliorates Experimental Asthma J. Immunol., October 1, 2001; 167(7): 3792 - 3799. [Abstract] [Full Text] [PDF] |
||||
![]() |
I. Gursel, M. Gursel, K. J. Ishii, and D. M. Klinman Sterically Stabilized Cationic Liposomes Improve the Uptake and Immunostimulatory Activity of CpG Oligonucleotides J. Immunol., September 15, 2001; 167(6): 3324 - 3328. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. Mui, S. G. Raney, S. C. Semple, and M. J. Hope Immune Stimulation by a CpG-Containing Oligodeoxynucleotide Is Enhanced When Encapsulated and Delivered in Lipid Particles J. Pharmacol. Exp. Ther., September 1, 2001; 298(3): 1185 - 1192. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. H. Baek, S. J. Ha, and Y. C. Sung A Novel Function of Phosphorothioate Oligodeoxynucleotides as Chemoattractants for Primary Macrophages J. Immunol., September 1, 2001; 167(5): 2847 - 2854. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. E. Britigan, T. S. Lewis, M. Waldschmidt, M. L. McCormick, and A. M. Krieg Lactoferrin Binds CpG-Containing Oligonucleotides and Inhibits Their Immunostimulatory Effects on Human B Cells J. Immunol., September 1, 2001; 167(5): 2921 - 2928. [Abstract] [Full Text] [PDF] |
||||
![]() |
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., August 1, 2001; 13(8): 1013 - 1020. [Abstract] [Full Text] [PDF] |
||||
![]() |
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., March 15, 2001; 166(6): 3743 - 3748. [Abstract] [Full Text] [PDF] |
||||
![]() |
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., February 15, 2001; 166(4): 2372 - 2377. [Abstract] [Full Text] [PDF] |
||||
![]() |
F.-G. Zhu and J. S. Marshall CpG-containing oligodeoxynucleotides induce TNF-{alpha} and IL-6 production but not degranulation from murine bone marrow-derived mast cells J. Leukoc. Biol., February 1, 2001; 69(2): 253 - 262. [Abstract] [Full Text] |
||||
![]() |
C. L. S. George, H. Jin, C. L. Wohlford-Lenane, M. E. O'Neill, J. C. Phipps, P. O'Shaughnessy, J. N. Kline, P. S. Thorne, and D. A. Schwartz Endotoxin responsiveness and subchronic grain dust-induced airway disease Am J Physiol Lung Cell Mol Physiol, February 1, 2001; 280(2): L203 - L213. [Abstract] [Full Text] [PDF] |
||||
![]() |
Z. Peng, H. Wang, X. Mao, K. T. HayGlass, and F. E. R. Simons CpG oligodeoxynucleotide vaccination suppresses IgE induction but may fail to down-regulate ongoing IgE responses in mice Int. Immunol., January 1, 2001; 13(1): 3 - 11. [Abstract] [Full Text] [PDF] |
||||
![]() |
T.-J. Huang, P. A. MacAry, P. Eynott, A. Moussavi, K. C. Daniel, P. W. Askenase, D. M. Kemeny, and K. F. Chung Allergen-Specific Th1 Cells Counteract Efferent Th2 Cell-Dependent Bronchial Hyperresponsiveness and Eosinophilic Inflammation Partly Via IFN-{{gamma}} J. Immunol., January 1, 2001; 166(1): 207 - 217. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. Serebrisky, A. A. Teper, C.-K. Huang, S.-Y. Lee, T.-F. Zhang, B. H. Schofield, M. Kattan, H. A. Sampson, and X.-M. Li 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., November 15, 2000; 165(10): 5906 - 5912. [Abstract] [Full Text] [PDF] |
||||
![]() |
F. Meyer, K. T. Wilson, and S. P. James Modulation of Innate Cytokine Responses by Products of Helicobacter pylori Infect. Immun., November 1, 2000; 68(11): 6265 - 6272. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. Miyazaki, G. Liu, L. Clark, and S. J. Ono Prevention of Acute Allergic Conjunctivitis and Late-Phase Inflammation with Immunostimulatory DNA Sequences Invest. Ophthalmol. Vis. Sci., November 1, 2000; 41(12): 3850 - 3855. [Abstract] [Full Text] |
||||
![]() |
G. J. Weiner The immunobiology and clinical potential of immunostimulatory CpG oligodeoxynucleotides J. Leukoc. Biol., October 1, 2000; 68(4): 455 - 463. [Abstract] [Full Text] |
||||
![]() |
S. W. Lee, M. K. Song, K. H. Baek, Y. Park, J. K. Kim, C. H. Lee, H.-K. Cheong, C. Cheong, and Y. C. Sun |