title: 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: 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.
authors.affiliation: Laboratory of Cellular Physiology and Immunology and Christopher H. Browne Center for Immunology and Immune Diseases, The Rockefeller University, New York, New York, United States of America.
authors.forename: Austin
authors.initials: A
authors.lastname: Pantel
authors.affiliation: Laboratory of Cellular Physiology and Immunology and Christopher H. Browne Center for Immunology and Immune Diseases, The Rockefeller University, New York, New York, United States of America.
authors.forename: Angela
authors.initials: A
authors.lastname: Teixeira
authors.affiliation: Vaccine and Gene Therapy Institute of Florida, Port St. Lucie, Florida, United States of America.
authors.forename: Elias
authors.initials: E
authors.lastname: Haddad
authors.affiliation: William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary, University of London, London, United Kingdom.
authors.forename: Elizabeth G
authors.initials: EG
authors.lastname: Wood
authors.affiliation: Laboratory of Cellular Physiology and Immunology and Christopher H. Browne Center for Immunology and Immune Diseases, The Rockefeller University, New York, New York, United States of America.
authors.forename: Ralph M
authors.initials: RM
authors.lastname: Steinman
authors.affiliation: Laboratory of Cellular Physiology and Immunology and Christopher H. Browne Center for Immunology and Immune Diseases, The Rockefeller University, New York, New York, United States of America ; William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary, University of London, London, United Kingdom.
authors.forename: M Paula
authors.initials: MP
authors.lastname: Longhi
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D017951:Antigen Presentation; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000276:immunology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology*; D006019:Glycolysis / Q000187:drug effects*; D007113:Immunity, Innate; D007274:Injections, Intraperitoneal; D000072640:Interferon-Induced Helicase, IFIH1; D016898:Interferon-alpha / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010085:Oxidative Phosphorylation / Q000187:drug effects*; D011070:Poly I-C / Q000494:pharmacology*; D015398:Signal Transduction; D051196:Toll-Like Receptor 3 / Q000235:genetics / Q000276:immunology; D014158:Transcription, Genetic
chemical_list: D016898:Interferon-alpha; C519703:TLR3 protein, mouse; D051196:Toll-Like Receptor 3; C510592:Ifih1 protein, mouse; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1; D011070:Poly I-C