title: Signaling through Toll-like receptor 3 and Dectin-1 potentiates the capability of human monocyte-derived dendritic cells to promote T-helper 1 and T-helper 17 immune responses.
abstract: OBJECTIVE
  Recent studies have shown that the ligation of Toll-like receptor 3 (TLR3) or Dectin-1 on human monocyte-derived dendritic cells (MoDC) elicits their maturation, but with a different outcome on immunomodulation. Therefore the aim of this work was to study the response of MoDC to the combined effect of polyinosinic:polycytydilic acid [Poly (I:C)] and curdlan, selective TLR3 and Dectin-1 agonists, respectively.
  
  
  METHODS
  Immature MoDC, generated from human monocytes, were treated with Poly (I:C), curdlan or their combination for 2 days. Phenotypic characteristics of MoDC were determined by flow cytometry, and cytokine production was measured by enzyme-linked immunosorbent assay (ELISA) and FlowCytomix, while the stimulatory capability of MoDC was tested using a mixed leukocyte reaction assay.
  
  
  RESULTS
  The combination of Poly (I:C) and curdlan induced phenotypic maturation of MoDC with the capability to stimulate an alloreactive response. Such treated MoDC up-regulated the production of interleukin (IL)-12, IL-23 and IL-10, compared with the effect of Poly (I:C) alone. Curdlan-treated MoDC stimulated the production of IL-17 by alloreactive CD4 (+) T cells more strongly than Poly (I:C)-treated MoDC. The opposite effect was observed for interferon(IFN)-γ production. When combined, these agonists primed MoDC to increase further the production of IFN-γ by CD4 (+) T cells in co-culture, especially those of naive (CD45RA (+)) phenotype, and IL-17 by memory (CD45RO (+)) CD4 (+) T cells.
  
  
  CONCLUSIONS
  Ligation of TLR3 and Dectin-1 receptor up-regulates T-helper (Th) 1 and Th17 immune responses compared with single agonists. These findings may have therapeutic implications for the use of MoDC in immunotherapy.
authors.affiliation: Military Medical Academy, Institute for Medical Research, Belgrade, Serbia.
authors.forename: Ana
authors.initials: A
authors.lastname: Dragicevic
authors.forename: Tanja
authors.initials: T
authors.lastname: Dzopalic
authors.forename: Sasa
authors.initials: S
authors.lastname: Vasilijic
authors.forename: Dragana
authors.initials: D
authors.lastname: Vucevic
authors.forename: Sergej
authors.initials: S
authors.lastname: Tomic
authors.forename: Biljana
authors.initials: B
authors.lastname: Bozic
authors.forename: Miodrag
authors.initials: M
authors.lastname: Colic
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000032:analysis; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D004357:Drug Synergism; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D037181:Lectins, C-Type / Q000819:agonists / Q000378:metabolism*; D009000:Monocytes / Q000276:immunology; D011069:Poly I / Q000494:pharmacology; D015398:Signal Transduction / Q000276:immunology; D018417:Th1 Cells / Q000187:drug effects* / Q000276:immunology; D058504:Th17 Cells / Q000187:drug effects* / Q000276:immunology; D051196:Toll-Like Receptor 3 / Q000819:agonists / Q000378:metabolism*; D047071:beta-Glucans / Q000494:pharmacology; D000099181:Dectin-1
chemical_list: D016207:Cytokines; D037181:Lectins, C-Type; D011069:Poly I; D051196:Toll-Like Receptor 3; D047071:beta-Glucans; C546929:CLEC7A protein, human; D000099181:Dectin-1; C495344:TLR3 protein, human; C038459:curdlan