Open AccessPhosphate-modified CpG oligonucleotides induce in vitro maturation of human myeloid dendritic cells
Author(s) -
А. А. Останин,
О. Ю. Леплина,
Е. А. Буракова,
Т. В. Тыринова,
А. А. Фокина,
Anastasia S. Proskurina,
Sergey S. Bogachev,
Dmitry A. Stetsenko,
Е. Р. Черных
Publication year - 2020
Publication title -
vavilovskij žurnal genetiki i selekcii
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.188
H-Index - 7
eISSN - 2500-0462
pISSN - 2500-3259
DOI - 10.18699/vj20.659
Subject(s) - cpg oligodeoxynucleotide , tlr9 , cpg site , chemistry , dendritic cell , thiophosphate , immune system , microbiology and biotechnology , immunology , biology , biochemistry , gene expression , dna methylation , gene , organic chemistry
Myeloid dendritic cells (DCs) play an important role in the immune response; therefore, the search for compounds that can effectively activate DCs is a needful goal. This study was aimed to investigate the effect of synthetic CpG oligodeoxynucleotides (CpG-ODN) on the maturation and allostimulatory activity of myeloid DCs in comparison with other PAMP and DAMP molecules. For the research, we synthesized known CpG-ODN class C (SD-101 and D-SL03) containing thiophosphate internucleotide groups, and their original phosphate-modified analogues (SD-101M and D- SL03M) with mesylphosphoramide internucleotide groups (M = μ-modification). The effects of CpG-ODN and other activators were evaluated on DCs generated from blood monocytes in the presence of GM-CSF and IFN-α (IFN-DC) or IL-4 (IL4-DC). Evaluation of the intracellular TLR-9 expression showed that both types of DCs (IFN-DC and IL4-DC) contained on average 52 and 80 % of TLR-9-positive cells, respectively. The CpG-ODNs studied enhanced the allostimulatory activity of IFN-DCs, and the effect of μ-modified CpG-ODNs was higher than that of CpG-ODNs with thiophosphate groups. The stimulating effect of CpG-ODN at a dose of 1.0 μg/ml was comparable (for D-SL03, D-SL03M, SD-101) with or exceeded (for SD-101M) the effect of LPS at a dose of 10 μg/ml. At the same time, IFN-DCs were characterized by greater sensitivity to the action of CpG-ODNs than IL4-DCs. The enhancement of DC allostimulatory activity in the presence of CpG-ODNs was associated with the induction of final DC maturation, which was confirmed by a significant decrease in the number of CD14+DC, an increase in mature CD83+DC and a trend towards an increase in CD86+DC. Interestingly, the characteristic ability of LPS to enhance the expression of the co-stimulatory molecule OX40L on DCs was revealed only for the μ-analogue SD-101M. In addition, CpG-ODNs (SD-101 and SD-101M) had a stimulatory effect on IFN-γ production comparable to the action of LPS. The data obtained indicate a stimulating effect of CpG-ODN on the maturation and allostimulatory activity of human myeloid DCs, which is more pronounced for μ-modified analogs.