A palindromic CpG-containing phosphodiester oligodeoxynucleotide as a mucosal adjuvant stimulates plasmacytoid dendritic cell-mediated T(H)1 immunity
| العنوان: | A palindromic CpG-containing phosphodiester oligodeoxynucleotide as a mucosal adjuvant stimulates plasmacytoid dendritic cell-mediated T(H)1 immunity |
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| المؤلفون: | Ayumi Kubota, Ichiroh Shimada, Saburo Yamamoto, Takasumi Matsuki, Youko Osawa, Eri Murata, Satomi Horiguchi, Takako Komiya, Jun-ichi Maeyama, Fumiko Suzuki, Masanori Isaka, Hisakazu Takatsuka, Sumiko Iho, Harukazu Kitagawa |
| المصدر: | PLoS ONE, Vol 9, Iss 2, p e88846 (2014) PLoS ONE |
| بيانات النشر: | Public Library of Science (PLoS), 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Diphtheria Toxoid, lcsh:Medicine, Plasmacytoid dendritic cell, Adaptive Immunity, Immunoglobulin E, Mice, lcsh:Science, Immune Response, Mice, Inbred BALB C, Multidisciplinary, biology, T Cells, Vaccination, hemic and immune systems, Infectious Diseases, Oligodeoxyribonucleotides, CpG site, Cytokines, Medicine, Female, Research Article, DNA, Bacterial, CpG Oligodeoxynucleotide, Immune Cells, Immunology, Bone Marrow Cells, Microbiology, Peripheral blood mononuclear cell, Immune Activation, Immune system, Adjuvants, Immunologic, Vaccine Development, Animals, Humans, Biology, Immunity to Infections, Adjuvants, Pharmaceutic, Diphtheria toxin, Mucous Membrane, lcsh:R, Immunity, Interferon-alpha, Immune Defense, Dendritic Cells, Th1 Cells, Mice, Inbred C57BL, Immune System, Leukocytes, Mononuclear, biology.protein, Clinical Immunology, lcsh:Q |
| الوصف: | Background CpG oligodeoxynucleotides (ODNs), resembling bacterial DNA, are currently tested in clinical trials as vaccine adjuvants. They have the nuclease-resistant phosphorothioate bond; the immune responses elicited differ according to the CpG ODN sequence and vaccination method. To develop a CpG ODN that can induce plasmacytoid dendritic cell (pDC)-mediated TH1 immunity through the mucosa, we constructed phosphodiester G9.1 comprising one palindromic CpG motif with unique polyguanosine-runs that allows degradation similar to naturally occurring bacterial DNA. Methods TH1 and TH2 immunity activation was evaluated by cytokine production pattern and T-bet/GATA-3 ratio in human peripheral blood mononuclear cells and mouse bone marrow cells. Adjuvanticity was evaluated in mice administered G9.1 with diphtheria toxoid (DT) through nasal vaccination. Results G9.1 exhibited stronger IFN-α-inducing activity than A-class CpG ODN2216 and increased T-bet/GATA-3 ratio by enhancing T-bet expression. Nasally administered G9.1 plus DT induced DT-specific mucosal IgA and serum IgG, but not IgE, responses with antitoxin activity in C57BL/6 and BALB/c mice, possibly due to IFN/BAFF production. Induction of TH1, but not TH2, -type Abs depended completely on pDCs, the first in vivo demonstration by CpG ODNs. Conclusions G9.1 is a promising mucosal adjuvant for induction of pDC-mediated TH1 immunity. |
| اللغة: | English |
| تدمد: | 1932-6203 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::76413f9eb526434ee7570ce58ca34c0d http://europepmc.org/articles/PMC3933336?pdf=render |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....76413f9eb526434ee7570ce58ca34c0d |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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