Vaccination with plasmid DNA activates dendritic cells via Toll-like receptor 9 (TLR9) but functions in TLR9-deficient mice.
We analyzed whether the immunobiology of vaccinating plasmid DNA containing a transcription unit for OVA is influenced by immunostimulatory CpG motifs in the plasmid backbone. Indeed, plasmid DNA differentially activated in vitro myeloid and plasmacytoid dendritic cells (DCs) provided they expressed the CpG-DNA receptor, Toll-like receptor 9 (TLR9). Dependent on the DC subset, activation resulted in type 1 IFN production, while both DC subsets produced IL-6 and up-regulated expression of costimulatory molecules CD40 and CD86. In vivo, however, even upon repeated vaccination with plasmid DNA, priming of OVA-specific CTL and clonal expansion of SIINFEKL-specific CD8 T cells were equal in TLR9-positive and TLR9- or MyD88-negative mice. Overall, these results negate a dominant role of CpG-DNA/TLR9 interactions in long-term vaccination protocols.
Spies
Barbara
B
Institute of Medical Microbiology, Immunology, and Hygiene, Technische Universität München, Munich, Germany.
Hochrein
Hubertus
H
Vabulas
Martin
M
Huster
Katharina
K
Busch
Dirk H
DH
Schmitz
Frank
F
Heit
Antje
A
Wagner
Hermann
H
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D045744:Cell Line, Tumor; D002469:Cell Separation; D002478:Cells, Cultured; D018899:CpG Islands / Q000276:immunology; D004268:DNA-Binding Proteins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D004527:Egg Proteins / Q000008:administration & dosage / Q000276:immunology; D007279:Injections, Subcutaneous; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008934:Mitogens / Q000008:administration & dosage / Q000276:immunology; D022423:Myeloid Cells / Q000276:immunology / Q000378:metabolism; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage / Q000276:immunology; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D010446:Peptide Fragments; D010957:Plasmids; D011956:Receptors, Cell Surface / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*; D051217:Toll-Like Receptor 9; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000276:immunology*
D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; D004268:DNA-Binding Proteins; D004527:Egg Proteins; D008934:Mitogens; C110366:OVA-8; D009838:Oligodeoxyribonucleotides; D010446:Peptide Fragments; D011956:Receptors, Cell Surface; C495370:Tlr9 protein, mouse; D051217:Toll-Like Receptor 9; D019444:Vaccines, DNA; D010047:Ovalbumin