Eat Dirt: CpG DNA and Immunomodulation of Asthma
- 1 July 2007
- journal article
- review article
- Published by American Thoracic Society in Proceedings of the American Thoracic Society
- Vol. 4 (3), 283-288
- https://doi.org/10.1513/pats.200701-019AW
Abstract
Asthma is a disorder of increasing prevalence and severity that has been linked with reduced early-life exposure to microbes and microbial products. Populations with increased environmental exposures to pathogen-associated molecular patterns (e.g., children who have large numbers of older siblings, who were raised on farms, and who have earlier out-of-home day-care attendance) have fewer and less severe atopic disorders. The mechanism(s) responsible for these observations remain uncertain, but modulation by pathogen-associated molecular patterns of the inflammatory milieu (and thus the setting in which allergens may be encountered) has received strong support. One microbial product with marked immunostimulatory properties is bacterial DNA, which differs from mammalian DNA in the frequency of cytosine-guanine (CpG) dinucleotides; many of the effects of bacterial DNA can be recapitulated by oligodeoxynucleotides (ODNs) containing CpG in specific base sequence motifs (CpG ODNs). Because CpG ODNs induce Th1-type cytokines (which can suppress the Th2-type responses that cause many of the manifestations of allergic disease), we speculated that they may be useful in preventing or reversing the eosinophilic inflammation of atopic asthma. We found this to be the case, using murine models of incipient and established allergic asthma, but learned that the Th1-type cytokines were not critical for efficacy. Subsequent work has suggested that induction of regulatory-type responses (from T cells and antigen-presenting cells) is involved in the protection provided by CpG ODNs. Ongoing clinical trials are examining the utility of CpG ODNs alone and as an adjuvant for immunotherapy in human populations with atopic disease.Keywords
This publication has 60 references indexed in Scilit:
- Synergistic Up-Regulation of Vascular Endothelial Growth Factor (VEGF) Expression in Macrophages by Adenosine A2AReceptor Agonists and Endotoxin Involves Transcriptional Regulation via the Hypoxia Response Element in the VEGF PromoterMolecular Biology of the Cell, 2007
- The inflammatory caspases: guardians against infections and sepsisCell Death & Differentiation, 2006
- Modulation of Airway Inflammation by Immunostimulatory CpG Oligodeoxynucleotides in a Murine Model of Allergic AspergillosisInfection and Immunity, 2004
- Selective immune redirection in humans with ragweed allergy by injecting Amb a 1 linked to immunostimulatory DNAJournal of Allergy and Clinical Immunology, 2004
- Exposure to farming in early life and development of asthma and allergy: a cross-sectional surveyThe Lancet, 2001
- Immunostimulatory sequence DNA linked to the Amb a 1 allergen promotes TH1 cytokine expression while downregulating TH2 cytokine expression in PBMCs from human patients with ragweed allergyJournal of Allergy and Clinical Immunology, 2001
- Siblings, Day-Care Attendance, and the Risk of Asthma and Wheezing during ChildhoodNew England Journal of Medicine, 2000
- Role of Transforming Growth Factor β in Human DiseaseNew England Journal of Medicine, 2000
- Predominant TH2-like Bronchoalveolar T-Lymphocyte Population in Atopic AsthmaNew England Journal of Medicine, 1992
- Hay fever, hygiene, and household size.BMJ, 1989