CpG oligodeoxynucleotides as TLR9 agonists: therapeutic application in allergy and asthma.
Unmethylated cytosine-phosphate-guanine (CpG) dinucleotides in microbial DNA sequences activate Toll-like receptor (TLR) 9, and previous studies have shown that oligodeoxynucleotides (ODNs) containing CpG in specific base sequence motifs (CpG ODNs) can reiterate the majority of the immunomodulatory effects produced by bacterial DNA. Many of the manifestations in allergic diseases are primarily due to T helper (T(h))-2 cell-type responses. CpG ODNs can induce T(h)1 and T-regulatory (T(reg)) cell-type cytokines that can suppress the T(h)2 response. The therapeutic application of TLR9 has been explored extensively in recent years, and many studies are being conducted to assess the safety and efficacy of TLR9 agonists in various diseases, including atopic and infectious diseases, and cancer. Studies in murine models have shown that the development of atopic airway disease can be prevented by treatment with CpG ODNs. Various clinical trials are currently ongoing to determine the efficacy of CpG ODNs as a therapeutic tool for atopic diseases. In this review, we discuss the therapeutic application of CpG ODNs in allergy and asthma. CpG ODNs may be used alone or as an adjuvant to immunotherapy to treat these disorders.
Gupta
Gaurav K
GK
Center for Clinical and Translational Science, Department of Biomedical Sciences, Creighton University School of Medicine, Omaha, Nebraska 68178, USA.
Agrawal
Devendra K
DK
D000276:Adjuvants, Immunologic; D000818:Animals; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D006967:Hypersensitivity / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D006969:Hypersensitivity, Immediate / Q000188:drug therapy* / Q000276:immunology; D007113:Immunity, Innate; D009838:Oligodeoxyribonucleotides / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use*; D018417:Th1 Cells / Q000276:immunology; D051217:Toll-Like Receptor 9 / Q000819:agonists* / Q000235:genetics / Q000276:immunology
D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; D009838:Oligodeoxyribonucleotides; D051217:Toll-Like Receptor 9