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

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.

Key Words::

• Dectin-1 receptor
• human monocyte-derived dendritic cells
• T-helper immune response
• Toll-like receptor 3

Acknowledgments

This study was supported by a grant (VMA/06 - 10/A.5) of the Military Medical Academy, Belgrade and Ministry of Science and Technological development R. Serbia (project number 175102). The authors thank Ivana Majstorovic and Katarina Lakovic for helpful assistance.

Disclosure of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.