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PMID: 16135562 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

The adjuvant activity of CpG DNA requires T-bet expression in dendritic cells.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 102 ·No. 37 ·2005-09-13 ·Pages 13248-53

Lugo-Villarino G, Ito S, Klinman DM, Glimcher LH

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.

MeSH Terms
Adoptive Transfer Animals CpG Islands DNA-Binding Proteins/deficiency Dendritic Cells/immunology,metabolism,transplantation Immunity, Innate Interferons/biosynthesis Listeria monocytogenes Listeriosis/therapy Mice Mice, Knockout Oligodeoxyribonucleotides/pharmacology T-Box Domain Proteins Transcription Factors/deficiency,immunology,physiology
Chemicals
CPG-oligonucleotide DNA-Binding Proteins Oligodeoxyribonucleotides Rag2 protein, mouse T-Box Domain Proteins T-box transcription factor TBX21 Transcription Factors V(D)J recombination activating protein 2 Interferons
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Lugo-Villarino Geanncarlo
Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115-6017, USA.
Ito Shu-Ichi
Klinman Dennis M
Glimcher Laurie H
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0506638102
Published
2005-09-13
Epub
2005-00-31
Pages
13248-53
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC1201626
Subset
IM
Grants
NIAID NIH HHS · P01 AI056296 · United States
NIAID NIH HHS · P01AI056296 · United States
External Links
PubMed source DOI: 10.1073/pnas.0506638102 PMC Full Text View journal details
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