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

Overview

Journal PLoS Biol

Specialty Biology

Date 2014 Jan 11

PMID 24409099

Citations 116

Authors

Austin Pantel

Angela Teixeira

Elias Haddad

Elizabeth G Wood

Ralph M Steinman

M Paula Longhi

Affiliations

Soon will be listed here.

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.

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