Type 1 Interferons Induce Changes in Core Metabolism that Are Critical for Immune Function

Duojiao Wu; David E Sanin; Bart Everts; Qiongyu Chen; Jing Qiu; Michael D Buck; Annette Patterson; Amber M Smith; Chih-Hao Chang; Zhiping Liu; Maxim N Artyomov; Erika L Pearce; Marina Cella; Edward J Pearce

doi:10.1016/j.immuni.2016.06.006

Type 1 Interferons Induce Changes in Core Metabolism that Are Critical for Immune Function

Immunity. 2016 Jun 21;44(6):1325-36. doi: 10.1016/j.immuni.2016.06.006.

Authors

Affiliations

¹ Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA; Zhongshan Hospital, Fudan University, Shanghai 200032, China.
² Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, 79108 Freiburg, Germany.
³ Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Parasitology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, the Netherlands.
⁴ Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
⁵ Department of Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, 79108 Freiburg, Germany.
⁶ Department of Biomedical Engineering, Shandong University, Jinan, Shandong 250061, China.
⁷ Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, 79108 Freiburg, Germany; Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany. Electronic address: [email protected].

Abstract

Greater understanding of the complex host responses induced by type 1 interferon (IFN) cytokines could allow new therapeutic approaches for diseases in which these cytokines are implicated. We found that in response to the Toll-like receptor-9 agonist CpGA, plasmacytoid dendritic cells (pDC) produced type 1 IFNs, which, through an autocrine type 1 IFN receptor-dependent pathway, induced changes in cellular metabolism characterized by increased fatty acid oxidation (FAO) and oxidative phosphorylation (OXPHOS). Direct inhibition of FAO and of pathways that support this process, such as fatty acid synthesis, prevented full pDC activation. Type 1 IFNs also induced increased FAO and OXPHOS in non-hematopoietic cells and were found to be responsible for increased FAO and OXPHOS in virus-infected cells. Increased FAO and OXPHOS in response to type 1 IFNs was regulated by PPARα. Our findings reveal FAO, OXPHOS and PPARα as potential targets to therapeutically modulate downstream effects of type 1 IFNs.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, N.I.H., Extramural

MeSH terms

3-Hydroxyacyl CoA Dehydrogenases / metabolism
Acetyl-CoA C-Acyltransferase / metabolism
Animals
Carbon-Carbon Double Bond Isomerases / metabolism
Cell Differentiation
Cells, Cultured
CpG Islands / immunology
Dendritic Cells / immunology*
Enoyl-CoA Hydratase / metabolism
Gene Expression Regulation
Immunity
Interferon Type I / metabolism*
Lipid Metabolism
Lymphocytic Choriomeningitis / immunology*
Lymphocytic choriomeningitis virus / immunology*
Mice
Mice, Inbred C57BL
Oligodeoxyribonucleotides / immunology
Oxidative Phosphorylation
PPAR alpha / metabolism*
Racemases and Epimerases / metabolism
Receptors, Interferon / metabolism
Signal Transduction
Toll-Like Receptor 9 / metabolism

Substances

Interferon Type I
Oligodeoxyribonucleotides
PPAR alpha
Receptors, Interferon
Toll-Like Receptor 9
fatty acid oxidation complex
3-Hydroxyacyl CoA Dehydrogenases
Acetyl-CoA C-Acyltransferase
Enoyl-CoA Hydratase
Racemases and Epimerases
Carbon-Carbon Double Bond Isomerases

Abstract

Publication types

MeSH terms

Substances

Grants and funding