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The adjuvant activity of CpG DNA requires T-bet expression in dendritic cells
Author(s) -
Geanncarlo LugoVillarino,
Shu-Ichi Ito,
Dennis M. Klinman,
Laurie H. Glimcher
Publication year - 2005
Publication title -
proceedings of the national academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0506638102
Subject(s) - cpg oligodeoxynucleotide , cpg site , cd11c , adoptive cell transfer , dendritic cell , adjuvant , biology , innate immune system , immunity , immunology , microbiology and biotechnology , immune system , t cell , dna methylation , phenotype , gene expression , gene , biochemistry
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.

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