We thank the Rockefeller University Center for Clinical and Translational Science (UL1 TR000043 NCATS, NIH) for technical
support

A Le Bon

A Mancino

A Subramanian

Angela Teixeira

Austin Pantel

Avinash Bhandoola

B Everts

CM Krawczyk

CR Ruprecht

DK Finlay

Elias Haddad

Elizabeth G. Wood

GA Kolumam

GL Semenza

H Jonuleit

J Jantsch

J Waddell

J Wang

JA Imlay

JD Ahlers

JM Curtsinger

JW Schoggins

KA Frauwirth

LZ Shi

M Wu

M. Paula Longhi

MF van den Broek

MJ de Veer

MP Longhi

O Joffre

P Aichele

R Spirig

R Spörri

R Wobben

Ralph M. Steinman

RM Steinman

S Fujii

S Kim

SD Der

SM Santini

SY Zhang

T Bhandari

T Ito

T Luft

T Pfeiffer

W Kratky

W Zhao

WJ Lesterhuis

X Qu

Y Tsujimoto

PLoS Biology

PubMed

Crossref

<div><p>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<sup>+</sup> and CD4<sup>+</sup> 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.</p></div

Austin Pantel (506312)

Angela Teixeira (506313)

Elias Haddad (506314)

Elizabeth G. Wood (506315)

Ralph M. Steinman (49018)

M. Paula Longhi (506316)

The Francis Crick Institute

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

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

CiteSeerX

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

Pantel Austin

Teixeira Angela

Haddad Elias

Wood Elizabeth G.

Steinman Ralph M.

Longhi M. Paula

Public Library of Science (PLOS)

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

Elizabeth G Wood

Ralph M Steinman

M Paula Longhi

Directory of Open Access Journals

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.

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

Abstract

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The Francis Crick Institute

CiteSeerX

Public Library of Science (PLOS)

Directory of Open Access Journals

Crossref

Queen Mary Research Online