CpG DNA-triggered upregulation of TLR9 expression affects apoptosis and immune responses in human plasmacytoid dendritic cells isolated from chronic hepatitis B patients

Abstract

Plasmacytoid dendritic cells (pDCs) were treated with cytosine-phosphate-guanine (CpG) DNA, and cell apoptosis, signals and immune responses were measured to investigate the effects and mechanism of CpG DNA in pDCs from chronic hepatitis B patients. CpG DNA-stimulated pDCs secreted more IFN-α than the control pDCs. CpG DNA activated Toll-like receptor 9 (TLR9), thereby resulting in the upregulated expression of myeloid differentiation primary response gene 88 (MyD88), interferon regulatory factor 7 (IRF7) and nuclear factor kappa B (NF-κB). Furthermore, CpG DNA down-regulated apoptosis and promoted the expression of IFN-α, interleukin-12 (IL-12), IL-21, IL-26 and tumour necrosis factor-α (TNF-α) in pDCs. Following treatment with NF-κB inhibitor, pyrollidine dithiocarbamate (PDTC), the influence of CpG DNA on pDCs was inhibited. Our results suggest that CpG DNA may directly interfere with the function of pDCs through TLR9-mediated upregulation of MyD88, IRF7 and NF-κB expression, which can partially explain the activation of pDCs in chronic hepatitis B patients.

Keywords:

• pDCs
• CpG DNA
• TLR9
• apoptosis
• immune response

Ethics approval

This study conformed to the ethical guidelines of the 1975 Declaration of Helsinki. All patients provided written informed consent before the participation into the study.

Disclosure statement

The authors declare that they have no competing interests

Author contributions

BZ and TW carried out the studies, participated in collecting data, and drafted the manuscript. XW and YZ performed the statistical analysis and participated in its design. JL helped to draft the manuscript. All authors read and approved the final manuscript.

Availability of data and materials

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Additional information

Funding

This work was supported by grant from “the relativity study of peripheral blood dendritic cell and toll liked receptor expression with sustained virus reaction of INF-αantivirus in chronic hepatitis B” (No.201303107, Health Brueau of Henan Province, China) and “2019 joint construction project of Henan Provincial Health Committee and Ministry of health” (No.SB201901062).