Immunostimulation and anti-DNA antibody production by backbone modified CpG-DNA |
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Authors: | Dongbum Kim Jae Won Rhee Sanghoon Kwon Wern-Joo Sohn Younghee Lee Dae-Won Kim Doo-Sik Kim Hyung-Joo Kwon |
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Institution: | 1. Department of Immunology and Microbial Science, Scripps Research Institute, La Jolla, CA 92037, USA;2. Department of Genetics, Scripps Research Institute, La Jolla, CA 92037, USA;3. Shanghai Institute of Materia Medica, Shanghai, China;4. General Atomics, Diazyme Division, San Diego, CA, USA |
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Abstract: | Oligodeoxynucleotides containing immunostimulatory CpG motifs (CpG-DNA) have gained attention as potentially useful therapeutics. However, the phosphorothioate-modified CpG-DNAs (PS-ODN) can induce backbone-related side effects. Here, we compared the immunostimulatory activity of natural phosphodiester CpG-DNA (PO-ODN) from Mycobacterium bovis and PS-ODN in mice. Both PO-ODN and PS-ODN induced production of IL-12. PS-ODN increased spleen weights, spleen cell numbers, and the migration of macrophages into the peritoneal cavity in the mice in a CG sequence-dependent manner. PS-ODN induced anti-PS-ODN antibody production in the mice, and the PS-ODN-specific IgM was cross-reactive with other PS-ODNs in a CG sequence-independent manner. In contrast, PO-ODN did not affect on spleen weights, cell numbers, or IgM production. These results may provide an explanation for the side effects in immunotherapeutic application of PS-ODN. They also suggest that PO-ODN may be more optimal than PS-ODN to enhance innate immune responses without severe side effects. |
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