title: TLR9 pathway is involved in adjuvant effects of plasmid DNA-based vaccines.
abstract: The presence of unmethylated CpG motifs in bacterial plasmids is thought to provide necessary immunoadjuvant signals to DNA vaccination. We took advantage of CpG-unresponsive toll-like receptor 9 (TLR9) knock-out mice to study whether this pathway was required to generate immune responses to DNA vaccination. We compared two vectors, one encoding the surface glycoprotein C of pseudorabies virus shown to protect target animals against challenge, and the other encoding the cytoplasmic enzyme beta-galactosidase. In the absence of TLR9, bone marrow-derived dendritic cells lost their ability to secrete IL-12 and type I IFN in response not only to CpG as expected but also to the plasmids used for vaccination. In contrast, DNA vaccination experiments showed that TLR9-deficient mice were able to mount Th1-biased antigen-specific antibody and IFN-gamma responses, albeit at lower levels than normal mice. Thus, TLR9 signaling is not needed for eliciting T- and B-cell responses to DNA encoded antigens. However, TLR9 signaling tended to enhance plasmid-adjuvant effects on antigen-specific immune responses.
authors.affiliation: INRA, Unité de Virologie et Immunologie Moléculaires, 78350 Jouy-en-Josas, France.
authors.forename: Daniela
authors.initials: D
authors.lastname: Tudor
authors.forename: Catherine
authors.initials: C
authors.lastname: Dubuquoy
authors.forename: Valérie
authors.initials: V
authors.lastname: Gaboriau
authors.forename: François
authors.initials: F
authors.lastname: Lefèvre
authors.forename: Bernard
authors.initials: B
authors.lastname: Charley
authors.forename: Sabine
authors.initials: S
authors.lastname: Riffault
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000906:Antibodies / Q000032:analysis; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D003713:Dendritic Cells / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007111:Immunity, Cellular / Q000235:genetics / Q000276:immunology; D007114:Immunization; D007202:Indicators and Reagents; D007371:Interferon-gamma / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010957:Plasmids / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology*; D018417:Th1 Cells / Q000276:immunology; D051217:Toll-Like Receptor 9; D019444:Vaccines, DNA / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000906:Antibodies; D017931:DNA Primers; D004268:DNA-Binding Proteins; D007202:Indicators and Reagents; D011956:Receptors, Cell Surface; C495370:Tlr9 protein, mouse; D051217:Toll-Like Receptor 9; D019444:Vaccines, DNA; D007371:Interferon-gamma