Immunostimulation and anti-DNA antibody production by backbone modified CpG-DNA.
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.
Kim
Dongbum
D
Department of Microbiology, College of Medicine, Hallym University, Gangwon-do 200-702, Republic of Korea.
Rhee
Jae Won
JW
Kwon
Sanghoon
S
Sohn
Wern-Joo
WJ
Lee
Younghee
Y
Kim
Dae-Won
DW
Kim
Doo-Sik
DS
Kwon
Hyung-Joo
HJ
D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis* / Q000276:immunology; D002465:Cell Movement; D018899:CpG Islands / Q000276:immunology*; D004247:DNA / Q000276:immunology* / Q000494:pharmacology; D007114:Immunization; D018664:Interleukin-12 / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009163:Mycobacterium bovis / Q000235:genetics / Q000276:immunology; D054735:Phosphorothioate Oligonucleotides / Q000276:immunology* / Q000494:pharmacology; D013163:Splenomegaly / Q000276:immunology*
D000974:Antibodies, Antinuclear; D054735:Phosphorothioate Oligonucleotides; D018664:Interleukin-12; D004247:DNA