PMID:24409099

Citation	Pantel, A, Teixeira, A, Haddad, E, Wood, EG, Steinman, RM and Longhi, MP (2014) 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. PLoS Biol. 12:e1001759
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.
Links	PubMed PMC3883643 Online version:10.1371/journal.pbio.1001759
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Significance

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:INAR1		GO:0045351: type I interferon biosynthetic process	ECO:0000314:		P		Figures 1B-E: The majority of changes to regulation of genes were dependent on type I IFN and not PRR stimulation. Thus type I IFN can be concluded to be the main variable for which maturation and metabolic shift to glycolysis after poly IC stimulation relies on.	complete CACAO 9359

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