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

Cytotherapy. 2012 May;14(5):598-607. doi: 10.3109/14653249.2012.667873. Epub 2012 Mar 16.


Background aims: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology
  • Cytokines / analysis
  • Dendritic Cells / drug effects*
  • Dendritic Cells / immunology
  • Drug Synergism
  • Humans
  • Immunity, Cellular / drug effects
  • Lectins, C-Type / agonists
  • Lectins, C-Type / metabolism*
  • Monocytes / immunology
  • Poly I / pharmacology
  • Signal Transduction / immunology
  • Th1 Cells / drug effects*
  • Th1 Cells / immunology
  • Th17 Cells / drug effects*
  • Th17 Cells / immunology
  • Toll-Like Receptor 3 / agonists
  • Toll-Like Receptor 3 / metabolism*
  • beta-Glucans / pharmacology


  • CLEC7A protein, human
  • Cytokines
  • Lectins, C-Type
  • TLR3 protein, human
  • Toll-Like Receptor 3
  • beta-Glucans
  • Poly I
  • curdlan