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PLoS Biol. 2014 Jan;12(1):e1001759. doi: 10.1371/journal.pbio.1001759. Epub 2014 Jan 7.

Direct type I IFN but not MDA5/TLR3 activation of dendritic cells is required for maturation and metabolic shift to glycolysis after poly IC stimulation.

Author information

1
Laboratory of Cellular Physiology and Immunology and Christopher H. Browne Center for Immunology and Immune Diseases, The Rockefeller University, New York, New York, United States of America.
2
Vaccine and Gene Therapy Institute of Florida, Port St. Lucie, Florida, United States of America.
3
William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary, University of London, London, United Kingdom.
4
Laboratory of Cellular Physiology and Immunology and Christopher H. Browne Center for Immunology and Immune Diseases, The Rockefeller University, New York, New York, United States of America ; William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary, University of London, London, United Kingdom.

Abstract

Type I interferons (IFNs) play an important role in direct antiviral defense as well as linking the innate and adaptive immune responses. On dendritic cells (DCs), IFNs facilitate their activation and contribute to CD8(+) and CD4(+) T cell priming. However, the precise molecular mechanism by which IFNs regulate maturation and immunogenicity of DCs in vivo has not been studied in depth. Here we show that, after in vivo stimulation with the TLR ligand poly IC, IFNs dominate transcriptional changes in DCs. In contrast to direct TLR3/mda5 signaling, IFNs are required for upregulation of all pathways associated with DC immunogenicity. In addition, metabolic pathways, particularly the switch from oxidative phosphorylation to glycolysis, are also regulated by IFNs and required for DC maturation. These data provide evidence for a metabolic reprogramming concomitant with DC maturation and offer a novel mechanism by which IFNs modulate DC maturation.

PMID:
24409099
PMCID:
PMC3883643
DOI:
10.1371/journal.pbio.1001759
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

The authors have declared that no competing interests exist.

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