title: Cutting Edge: Critical Role of Glycolysis in Human Plasmacytoid Dendritic Cell Antiviral Responses.
abstract: Plasmacytoid dendritic cells (pDCs) are vital to antiviral defense, directing immune responses via secretion of huge concentrations of IFN-α. These cells are critical in protecting the lung against clinically relevant respiratory viruses, particularly influenza (Flu), a virus responsible for substantial worldwide morbidity and mortality. How pDC responses to such viral pathogens are regulated, however, is poorly understood in humans. Using an unbiased approach of gene chip analysis, we discovered that Flu significantly affects metabolism in primary human pDCs. We demonstrate that Flu and RV, another common respiratory virus, induce glycolysis in pDCs and that this metabolic pathway regulates pDC antiviral functions, including IFN-α production and phenotypic maturation. Intranasal vaccination of human volunteers with live influenza virus also increases glycolysis in circulating pDCs, highlighting a previously unrecognized potential role for metabolism in regulating pDC immune responses to viral infections in humans.
authors.affiliation: Division of Infectious Disease, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390; Division of Pulmonary and Vascular Biology, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390; Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390;
authors.forename: Gagan
authors.initials: G
authors.lastname: Bajwa
authors.affiliation: Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390; McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, TX 75390;
authors.forename: Ralph J
authors.initials: RJ
authors.lastname: DeBerardinis
authors.affiliation: Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390; and.
authors.forename: Baomei
authors.initials: B
authors.lastname: Shao
authors.affiliation: Amnis Corporation, Seattle, WA 98119.
authors.forename: Brian
authors.initials: B
authors.lastname: Hall
authors.affiliation: Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390;
authors.forename: J David
authors.initials: JD
authors.lastname: Farrar
authors.affiliation: Division of Infectious Disease, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390; Division of Pulmonary and Vascular Biology, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390; Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390; Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390; and michelle.gill@utsouthwestern.edu.
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Gill
mesh_terms: D000328:Adult; D002849:Chromatography, Gas; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D005434:Flow Cytometry; D006019:Glycolysis / Q000276:immunology*; D006801:Humans; D007252:Influenza Vaccines / Q000276:immunology; D007251:Influenza, Human / Q000276:immunology*; D016898:Interferon-alpha / Q000276:immunology; D008297:Male; D013058:Mass Spectrometry; D020411:Oligonucleotide Array Sequence Analysis; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D007252:Influenza Vaccines; D016898:Interferon-alpha
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