Methylated CpG-containing plasmid activates the immune system

被引：18

作者：

Cornélie, S ^{[1
]}

Poulain-Godefroy, O ^{[1
]}

Lund, C ^{[1
]}

Vendeville, C ^{[1
]}

Ban, E ^{[1
]}

Capron, M ^{[1
]}

Riveau, G ^{[1
]}

机构：

[1] Inst Pasteur, INSERM, U547, F-59019 Lille, France

来源：

SCANDINAVIAN JOURNAL OF IMMUNOLOGY | 2004年 / 59卷 / 02期

关键词：

D O I：

10.1111/j.0300-9475.2004.01373.x

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Bacterial DNA differs from mammalian DNA by the presence of unmethylated cytosine-phosphate-guanosine (CpG) motifs. The immunostimulatory properties of a DNA vaccine have been suspected to be associated with these motifs. The aim of this study was to assess the inactivation of the immunostimulatory potential of a plasmid after methylation of its CpG motifs. We constructed two identical non-coding plasmids, and one of these was de novo methylated on its CG sequences. A single administration of recombinant antigen with methylated or unmethylated CpG-containing plasmid was performed in mice. As expected, only unmethylated CpG-containing plasmid enhanced the specific immune response. However, a study of in vivo activation of Langerhans' cells and analysis of mRNA synthesis indicated that both the plasmids promoted cell emigration and cytokine induction. These data highlight that a methylated CpG-containing plasmid is not inert and carries immunomodulatory properties. The results further emphasize the necessity to definitively identify the mode of action of plasmids used for DNA vaccination.

引用

收藏

页码：143 / 151

页数：9

相关论文

共 50 条

[1] Cutaneous vaccination: the skin as an immunologically active tissue and the challenge of antigen delivery [J].

Babiuk, S ;

Baca-Estrada, M ;

Babiuk, LA ;

Ewen, C ;

Foldvari, M .

JOURNAL OF CONTROLLED RELEASE, 2000, 66 (2-3) :199-214

[2] CpG motifs induce Langerhans cell migration in vivo [J].

Ban, E ;

Dupré, L ;

Hermann, E ;

Rohn, W ;

Vendeville, C ;

Quatannens, B ;

Ricciardi-Castagnoli, P ;

Capron, A ;

Riveau, G .

INTERNATIONAL IMMUNOLOGY, 2000, 12 (06) :737-745

[3] Hsp90 binds CpG oligonucleotides directly:: implications for Hsp90 as a missing link in CpG signaling and recognition [J].

Bandholtz, L ;

Guo, Y ;

Palmberg, C ;

Mattsson, K ;

Ohlsson, B ;

High, A ;

Shabanowitz, J ;

Hunt, DF ;

Jörnvall, H ;

Wigzell, H ;

Agerberth, B ;

Gudmundsson, GH .

CELLULAR AND MOLECULAR LIFE SCIENCES, 2003, 60 (02) :422-429

[4] DNA activates human immune cells through a CpG sequence-dependent manner [J].

Bauer, M ;

Heeg, K ;

Wagner, H ;

Lipford, GB .

IMMUNOLOGY, 1999, 97 (04) :699-705

[5] Human TLR9 confers responsiveness to bacterial DNA via species-specific CpG motif recognition [J].

Bauer, S ;

Kirschning, CJ ;

Häcker, H ;

Redecke, V ;

Hausmann, S ;

Akira, S ;

Wagner, H ;

Lipford, GB .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (16) :9237-9242

[6] Lactoferrin binds CpG-containing oligonucleotides and inhibits their immunostimulatory effects on human B cells [J].

Britigan, BE ;

Lewis, TS ;

Waldschmidt, M ;

McCormick, ML ;

Krieg, AM .

JOURNAL OF IMMUNOLOGY, 2001, 167 (05) :2921-2928

[7] PERVASIVE CPG SUPPRESSION IN ANIMAL MITOCHONDRIAL GENOMES [J].

CARDON, LR ;

BURGE, C ;

CLAYTON, DA ;

KARLIN, S .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (09) :3799-3803

[8] Identification of methylated CpG motifs as inhibitors of the immune stimulatory CpG motifs [J].

Chen, Y ;

Lenert, P ;

Weeratna, R ;

McCluskie, M ;

Wu, T ;

Davis, HL ;

Krieg, AM .

GENE THERAPY, 2001, 8 (13) :1024-1032

[9]

Chuang TH, 2002, J LEUKOCYTE BIOL, V71, P538

[10] Cytosine-phosphate-guanine (CpG) motifs are sensitizing agents for lipopolysaccharide in toxic shock model [J].

Cornelie, S ;

Wiel, E ;

Lund, N ;

Lebuffe, G ;

Vendeville, C ;

Riveau, G ;

Vallet, B ;

Ban, E .

INTENSIVE CARE MEDICINE, 2002, 28 (09) :1340-1347

← 1 2 3 4 5 →