title: The adjuvant activity of CpG DNA requires T-bet expression in dendritic cells.
abstract: Treatment with synthetic oligodeoxynucleotides containing CpG motifs (CpG ODNs) is remarkably protective against otherwise lethal infection. Here, we describe an essential role for the transcription factor T-bet in mediating the protective function of CpG ODNs. Loss of T-bet in conventional CD11c(hi) dendritic cells (DCs) and in plasmacytoid DCs impaired production of IFNs. Strikingly, in contrast to Rag2-/- mice, Rag2-/- mice that also lacked T-bet (DKO) could not be rescued from lethal Listeria monocytogenes infection by prior treatment with CpG ODN. Rescue was achieved by adoptive transfer of CD11c(hi) DCs from WT, but not T-bet-/-, CpG ODN-treated donor mice. We conclude that T-bet in DCs is required for the adjuvant activity of CpG ODN in infection, revealing its vital role in innate immunity.
authors.affiliation: Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115-6017, USA.
authors.forename: Geanncarlo
authors.initials: G
authors.lastname: Lugo-Villarino
authors.forename: Shu-Ichi
authors.initials: S
authors.lastname: Ito
authors.forename: Dennis M
authors.initials: DM
authors.lastname: Klinman
authors.forename: Laurie H
authors.initials: LH
authors.lastname: Glimcher
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D018899:CpG Islands; D004268:DNA-Binding Proteins / Q000172:deficiency; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D007113:Immunity, Innate; D007372:Interferons / Q000096:biosynthesis; D008089:Listeria monocytogenes; D008088:Listeriosis / Q000628:therapy; D051379:Mice; D018345:Mice, Knockout; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D020825:T-Box Domain Proteins; D014157:Transcription Factors / Q000172:deficiency / Q000276:immunology / Q000502:physiology*; D000098815:T-bet Transcription Factor
chemical_list: C408982:CPG-oligonucleotide; D004268:DNA-Binding Proteins; D009838:Oligodeoxyribonucleotides; C499308:Rag2 protein, mouse; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D014157:Transcription Factors; C064655:V(D)J recombination activating protein 2; D007372:Interferons