title: Induction of IFNα or IL-12 depends on differentiation of THP-1 cells in dengue infections without and with antibody enhancement.
abstract: BACKGROUND
  Appropriate induction of the early Th1 cytokine IL-12 is a critical defense directed against viral infection. We have previously shown that different viruses elicited either IL-12 or IFNα dependent Th1 reactions. Using dengue-2 virus, we sought to explore how dengue-2 induced IL-12 or IFNα expression by monocytic and its derived dendritic cells.
  
  
  METHODS
  We employed human monocytic cell line, THP-1, to investigate whether differentiation of monocytic cells is involved in the switch between IFNα and IL-12 induction. Flow cytometry, RT-PCR and ELISA were respectively used to determine cell differentiation, IL-12 and IFNα mRNA expression and protein production.
  
  
  RESULTS
  THP-1, expressing CD123, which is a plasmacytoid dendritic cell marker, but not CD14, CD11b or CD11c revealed IFNα mRNA expression while stimulated by dengue-2. In contrast, PMA-induced THP-1 differentiation toward monocytic cells expressed CD11b+, and CD14+, but not CD123, and revealed exclusively IL-12 expression while stimulated by dengue-2. Further studies showed that CD123+ expressing THP-1 cells elicited higher IFNα expression in dose and time dependent induction after infection, and PMA-induced monocytic differentiation of THP-1 cells revealed IL-12 expression. Antibody-dependent enhancement of DEN-2 infection significantly suppressed the DEN-2 induced IL-12 p40 expression in monocytic differentiated THP-1 cells.
  
  
  CONCLUSIONS
  Clarification and modulation of the early Th1 reaction in different monocytic cells may change or prevent complication from dengue infection.
authors.affiliation: Department of Medical Research and Development, Show Chwan Health Care System, Changhua, Taiwan.
authors.forename: Rong-Fu
authors.initials: RF
authors.lastname: Chen
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.forename: Jiin-Tsuey
authors.initials: JT
authors.lastname: Cheng
authors.forename: Kuender D
authors.initials: KD
authors.lastname: Yang
mesh_terms: D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D003715:Dengue / Q000276:immunology* / Q000378:metabolism*; D003716:Dengue Virus / Q000276:immunology / Q000472:pathogenicity; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D016898:Interferon-alpha / Q000235:genetics / Q000378:metabolism*; D018664:Interleukin-12 / Q000235:genetics / Q000378:metabolism*; D053650:Interleukin-3 Receptor alpha Subunit / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D016898:Interferon-alpha; D053650:Interleukin-3 Receptor alpha Subunit; D018664:Interleukin-12