title: Differential responses of plasmacytoid dendritic cells to influenza virus and distinct viral pathogens.
abstract: Plasmacytoid dendritic cells (pDCs) are key components of the innate immune response that are capable of synthesizing and rapidly releasing vast amounts of type I interferons (IFNs), particularly IFN-α. Here we investigated whether pDCs, often regarded as a mere source of IFN, discriminate between various functionally discrete stimuli and to what extent this reflects differences in pDC responses other than IFN-α release. To examine the ability of pDCs to differentially respond to various doses of intact and infectious HIV, hepatitis C virus, and H1N1 influenza virus, whole-genome gene expression analysis, enzyme-linked immunosorbent assays, and flow cytometry were used to investigate pDC responses at the transcriptional, protein, and cellular levels. Our data demonstrate that pDCs respond differentially to various viral stimuli with significant changes in gene expression, including those involved in pDC activation, migration, viral endocytosis, survival, or apoptosis. In some cases, the expression of these genes was induced even at levels comparable to that of IFN-α. Interestingly, we also found that depending on the viral entity and the viral titer used for stimulation, induction of IFN-α gene expression and the actual release of IFN-α are not necessarily temporally coordinated. In addition, our data suggest that high-titer influenza A (H1N1) virus infection can stimulate rapid pDC apoptosis.
  
  
  OBJECTIVE
  Plasmacytoid dendritic cells (pDCs) are key players in the viral immune response. With the host response to viral infection being dependent on specific virus characteristics, a thorough examination and comparison of pDC responses to various viruses at various titers is beneficial for the field of virology. Our study illustrates that pDC infection with influenza virus, HIV, or hepatitis C virus results in a unique and differential response to each virus. These results have implications for future virology research, vaccine development, and virology as a whole.
authors.affiliation: Infectious Disease and Immunogenetics Section (IDIS), Department of Transfusion Medicine, CC, and Trans-NIH Center for Human Immunology (CHI), NIH, Bethesda, Maryland, USA.
authors.forename: Jaime M
authors.initials: JM
authors.lastname: Thomas
authors.affiliation: MTA-Semmelweis University "Lendület" Experimental and Translational Immunomics Research Group, Budapest, HungaryInfectious Disease and Immunogenetics Section (IDIS), Department of Transfusion Medicine, CC, and Trans-NIH Center for Human Immunology (CHI), NIH, Bethesda, Maryland, USA.
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Pos
authors.affiliation: Infectious Disease and Immunogenetics Section (IDIS), Department of Transfusion Medicine, CC, and Trans-NIH Center for Human Immunology (CHI), NIH, Bethesda, Maryland, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Reinboth
authors.affiliation: Infectious Disease and Immunogenetics Section (IDIS), Department of Transfusion Medicine, CC, and Trans-NIH Center for Human Immunology (CHI), NIH, Bethesda, Maryland, USA.
authors.forename: Richard Y
authors.initials: RY
authors.lastname: Wang
authors.affiliation: Infectious Disease and Immunogenetics Section (IDIS), Department of Transfusion Medicine, CC, and Trans-NIH Center for Human Immunology (CHI), NIH, Bethesda, Maryland, USA Sidra Medical and Research Centre, Doha, Qatar.
authors.forename: Ena
authors.initials: E
authors.lastname: Wang
authors.affiliation: Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA.
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Frank
authors.affiliation: Laboratory of Immunoregulation, Immunopathogenesis Section, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA.
authors.forename: Paolo
authors.initials: P
authors.lastname: Lusso
authors.affiliation: Laboratory of Experimental Immunology, Cancer Immunobiology Section, Frederick National Lab, Frederick, Maryland, USA.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Trinchieri
authors.affiliation: Infectious Disease and Immunogenetics Section (IDIS), Department of Transfusion Medicine, CC, and Trans-NIH Center for Human Immunology (CHI), NIH, Bethesda, Maryland, USA.
authors.forename: Harvey J
authors.initials: HJ
authors.lastname: Alter
authors.affiliation: Sidra Medical and Research Centre, Doha, QatarInfectious Disease and Immunogenetics Section (IDIS), Department of Transfusion Medicine, CC, and Trans-NIH Center for Human Immunology (CHI), NIH, Bethesda, Maryland, USA fmarincola@sidra.org ethomas1@med.miami.edu.
authors.forename: Francesco M
authors.initials: FM
authors.lastname: Marincola
authors.affiliation: Schiff Center for Liver Diseases, Sylvester Comprehensive Cancer Center, Department of Cell Biology, University of Miami Miller School of Medicine, Miami, Florida, USA fmarincola@sidra.org ethomas1@med.miami.edu.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Thomas
mesh_terms: D003713:Dendritic Cells / Q000276:immunology / Q000821:virology*; D015658:HIV Infections / Q000235:genetics / Q000276:immunology / Q000821:virology*; D015497:HIV-1 / Q000502:physiology*; D016174:Hepacivirus / Q000502:physiology*; D006526:Hepatitis C / Q000235:genetics / Q000276:immunology / Q000821:virology*; D006801:Humans; D007113:Immunity, Innate; D053118:Influenza A Virus, H1N1 Subtype / Q000502:physiology*; D007251:Influenza, Human / Q000235:genetics / Q000276:immunology / Q000821:virology*; D007370:Interferon Type I / Q000235:genetics / Q000276:immunology; D013045:Species Specificity; D059467:Transcriptome
chemical_list: D007370:Interferon Type I