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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adoptive Transfer
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Animals
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CpG Islands*
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DNA-Binding Proteins / deficiency
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Dendritic Cells / immunology*
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Dendritic Cells / metabolism
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Dendritic Cells / transplantation
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Immunity, Innate
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Interferons / biosynthesis
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Listeria monocytogenes
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Listeriosis / therapy
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Mice
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Mice, Knockout
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Oligodeoxyribonucleotides / pharmacology*
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T-Box Domain Proteins
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T-bet Transcription Factor
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Transcription Factors / deficiency
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Transcription Factors / immunology
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Transcription Factors / physiology*
Substances
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CPG-oligonucleotide
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DNA-Binding Proteins
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Oligodeoxyribonucleotides
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Rag2 protein, mouse
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T-Box Domain Proteins
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T-bet Transcription Factor
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Transcription Factors
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V(D)J recombination activating protein 2
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Interferons