title: Novel immunostimulatory phosphodiester oligodeoxynucleotides with CpT sequences instead of CpG motifs.
abstract: The innate immune system recognizes bacterial DNA as a nonself to induce rapid immune activation. TLR9 recognizes synthetic oligodeoxynucleotides (ODNs) and bacterial DNA containing unmethylated CpG dinucleotides in the context of specific base sequences (CpG-DNA). Here, we demonstrate that phosphorothioate backbone CT-ODN (PS-CT-ODN), a derivative of phosphorothioate backbone CpG-DNA (PS-ODN) with CT sequences substituted for the CG sequences, stimulates IL-8 promoter activation and gene expression. Furthermore, we identified an immunostimulatory phosphodiester bond CT-ODN (PO-CT-ODN) from Staphylococcus aureus chromosomal DNA and found that the PO-CT-ODN induces cytokine production in a TLR9-dependent manner when encapsulated with a proper liposome. Our experimental analyses also demonstrate that the immunostimulatory PO-CT-ODN can act as an adjuvant for the induction of Ag-driven IgG production. Further investigation of the functional role of PO-CT-ODN may support the future application of PO-CT-ODN in immunotherapeutics.
authors.affiliation: Department of Microbiology, College of Medicine, Hallym University, Gangwon-do 200-702, Republic of Korea.
authors.forename: Dongbum
authors.initials: D
authors.lastname: Kim
authors.forename: Jinwon
authors.initials: J
authors.lastname: Jung
authors.forename: Younghee
authors.initials: Y
authors.lastname: Lee
authors.forename: Hyung-Joo
authors.initials: HJ
authors.lastname: Kwon
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D001483:Base Sequence; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis; D004269:DNA, Bacterial / Q000276:immunology*; D015226:Dinucleoside Phosphates / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression; D006801:Humans; D007114:Immunization; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics; D008081:Liposomes; D051379:Mice; D008807:Mice, Inbred BALB C; D009838:Oligodeoxyribonucleotides / Q000276:immunology*; D054735:Phosphorothioate Oligonucleotides / Q000276:immunology*; D011401:Promoter Regions, Genetic; D013211:Staphylococcus aureus / Q000235:genetics / Q000276:immunology; D051217:Toll-Like Receptor 9 / Q000378:metabolism*
chemical_list: D000276:Adjuvants, Immunologic; D016207:Cytokines; D004269:DNA, Bacterial; D015226:Dinucleoside Phosphates; D007074:Immunoglobulin G; D016209:Interleukin-8; D008081:Liposomes; D009838:Oligodeoxyribonucleotides; D054735:Phosphorothioate Oligonucleotides; D051217:Toll-Like Receptor 9; C015772:CpG dinucleotide