Newly identified CpG ODNs, M5-30 and M6-395, stimulate mouse immune cells to secrete TNF-alpha and enhance Th1-mediated immunity.
Bacterial CpG motifs are known to induce both innate and adaptive immunity in infected hosts via toll-like receptor 9 (TLR9). Because small oligonucleotides (ODNs) mimicking bacterial CpG motifs are easily synthesized, they have found use as immunomodulatory agents in a number of disease models. We have developed a novel bioinformatics approach to identify effective CpG ODN sequences and evaluate their function as TLR9 ligands in a murine system. Among the CpG ODNs we identified, M5-30 and M6-395 showed significant ability to stimulate TNF-alpha and IFN-gamma production in a mouse macrophage cell line and mouse splenocytes, respectively. We also found that these CpG ODNs activated cells through the canonical NF-kappa B signaling pathway. Moreover, both CpG ODNs were able to induce Th1-mediated immunity in Mycobacterium tuberculosis (Mtb)-infected mice. Our results demonstrate that M5-30 and M6-395 function as TLR9-specific ligands, making them useful in the study of TLR9 functionality and signaling in mice.
Choi
Sun-Shim
SS
Department of Molecular and Medical Biotechnology, Kangwon National University, Chuncheon, Republic of Korea.
Chung
Eunkyung
E
Jung
Yu-Jin
YJ
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002478:Cells, Cultured; D006801:Humans; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D051379:Mice / Q000235:genetics / Q000276:immunology*; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000502:physiology; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D051217:Toll-Like Receptor 9 / Q000235:genetics / Q000276:immunology; D014376:Tuberculosis / Q000276:immunology / Q000382:microbiology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
C408982:CPG-oligonucleotide; D009838:Oligodeoxyribonucleotides; D051217:Toll-Like Receptor 9; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma
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