Response of human monocyte-derived dendritic cells to the combined effect of TLR3 and TLR7 agonists
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1
Faculty of Medicine, University of Nis, Serbia
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2
Medical Faculty of the Military Medical Academy, University of Defense in Belgrade, Serbia
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3
Faculty of Biology, Institute for Physiology and Biochemistry, University of Belgrade, Serbia
Targeting Toll-like receptors (TLRs) by specific agonists seems to be a promising in stimulation of the immunogenicity of dendritic cells (DCs). Since the functional outcome upon the activation of TLRs may be different, the aim of our study was to evaluate how different concentrations of 7-thia-8-oxo-guanosine (7-TOG), a selective TLR7 agonist, affects functional and phenotypic properties of human monocyte-derived DCs (MoDCs) and if they could be modulated by co-ligation of TLR3.
Immature MoDCs were treated with different concentrations of 7-TOG (25, 100 and 250 μmol/L) alone, or together with poly (I:C) (10 ng/mL), a selective TLR3 agonist.
We showed that the highest concentration of 7-TOG stimulated the differentiation, maturation and allostimulatory capability of MoDCs, which were accompanied by induction of T helper (Th)1 and Th17 immune responses. Both Th responses were significantly enhanced by additional stimulation of MoDCs with poly (I:C). Intermediate concentration of 7-TOG up-regulated the expression of CD86 and increased production of IL-1β and IL-6 by MoDCs, followed by the stimulation of Th17 immune response. The treatment of MoDCs with the lowest concentration of 7-TOG down-regulated the expression of CD40 on MoDCs and potentiated the Th2 immune response. Additional treatment of MoDCs with poly (I:C) also stimulated both Th1 and Th17 responses, whereas Th2 response was not significantly modulated.
In conclusion, our results show that 7-TOG influences phenotype and functions of MoDCs in a dose-dependent manner and suggests that signaling through TLR7 may be modified by the engagement of TLR3, resulting in a different outcome of immune response.
Acknowledgements
This study was supported by the project of Ministry of Science and Technological Development of the Republic of Serbia (project number 175102) and by a local grant of Military Medical Academy, Belgrade (VMA/06-10/A.3)
Keywords:
Monocyte-derived dendritic cells,
poly (I:C),
Toll-Like Receptor 3,
7-thia-8-oxo-guanosine,
Toll-Like Receptor 7
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Immune receptors and signaling
Citation:
Dzopalic
T,
Dragicevic
A,
Bozic
B,
Rajkovic
I and
Colic
M
(2013). Response of human monocyte-derived dendritic cells to the combined effect of TLR3 and TLR7 agonists.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.00131
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Received:
11 Mar 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Dr. Tanja Dzopalic, Faculty of Medicine, University of Nis, Nis, Serbia, tanjche80@gmail.com