Vaccination with Plasmid DNA Activates Dendritic Cells via Toll-Like Receptor 9 (TLR9) but Functions in TLR9-Deficient Mice

Barbara Spies, Hubertus Hochrein, Martin Vabulas, Katharina Huster, Dirk H. Busch, Frank Schmitz, Antje Heit, Hermann Wagner

Research output: Contribution to journalArticlepeer-review

184 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)5908-5912
Number of pages5
JournalJournal of Immunology
Volume171
Issue number11
DOIs
StatePublished - 1 Dec 2003

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