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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
Journal article   Open access   Peer reviewed

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

Austin Pantel, Angela Teixeira, Elias Haddad, Elizabeth G Wood, Ralph M Steinman and M Paula Longhi
PLoS biology, v 12(1), pp e1001759-e1001759
Jan 2014
DOI: https://doi.org/10.1371/journal.pbio.1001759
PMID: 24409099
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.1001759&type=printableView
Published, Version of Record (VoR) Open
url
https://doi.org/10.1371/journal.pbio.1001759View
Published, Version of Record (VoR) Open

Abstract

Adaptive Immunity Animals Antigen Presentation CD4-Positive T-Lymphocytes - drug effects CD4-Positive T-Lymphocytes - immunology CD4-Positive T-Lymphocytes - metabolism CD8-Positive T-Lymphocytes - drug effects CD8-Positive T-Lymphocytes - immunology CD8-Positive T-Lymphocytes - metabolism Cell Differentiation DEAD-box RNA Helicases - genetics DEAD-box RNA Helicases - immunology Dendritic Cells - drug effects Dendritic Cells - immunology Dendritic Cells - metabolism Gene Expression Profiling Gene Expression Regulation - drug effects Gene Expression Regulation - immunology Glycolysis - drug effects Immunity, Innate Injections, Intraperitoneal Interferon-alpha - genetics Interferon-alpha - immunology Interferon-Induced Helicase, IFIH1 Mice Mice, Inbred C57BL Mice, Transgenic Oxidative Phosphorylation - drug effects Poly I-C - pharmacology Signal Transduction Toll-Like Receptor 3 - genetics Toll-Like Receptor 3 - immunology Transcription, Genetic
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.

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Collaboration types
Domestic collaboration
International collaboration
Web of Science research areas
Biochemistry & Molecular Biology
Biology
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