Plasmacytoid Dendritic Cell Function and Cytokine Network Profiles in Patients with Acute or Chronic Hepatitis B Virus Infection

Abstract

Background:Plasmacytoid dendritic cells (pDCs) and cytokines play an important role in occurrence and recovery of hepatitis B virus (HBV) infection. The aim of this study was to explore the frequency and function of pDC and serum cytokine network profiles in patients with acute or chronic HBV infection.Methods:The healthy individuals (HI group), hepatitis B envelope antigen (HBeAg)-positive chronic HBV patients in immune tolerance (IT) phase (IT group), HBeAg-positive chronic HBV patients (CHB group), and acute HBV patients (AHB group) were enrolled in this study. The frequency of cluster of differentiation antigen 86 (CD86) + pDC and the counts of CD86 molecular expressed on surface of pDC were tested by flow cytometer. The quantitative determinations of cytokines, including Fms-like tyrosine kinase 3 ligand (Flt-3L), interferon (IFN)-α2, IFN-γ, interleukin (IL)-17A, IL-6, IL-10, transforming growth factor (TGF)-β1 and TGF-β2, were performed using Luminex multiplex technology.Results:In this study, there were 13 patients in HI group, 30 in IT group, 50 in CHB group, and 32 in AHB group. Compared with HI group, HBV infected group (including all patients in IT, CHB and AHB groups) had significantly higher counts of CD86 molecular expressed on the surface of pDC (4596.5 ± 896.5 vs. 7097.7 ± 3124.6; P < 0.001). The counts of CD86 molecular expressed on the surface of pDC in CHB group (7739.2 ± 4125.4) was significantly higher than that of IT group (6393.4 ± 1653.6, P = 0.043). Compared with IT group, the profile of cytokines of Flt-3L, IFN-γ, and IL-17A was decreased, IFN-α2 was significantly increased (P = 0.012) in CHB group. The contents of IL-10, TGF-β1, and TGF-β2 in AHB group were significantly increased compared with IT and CHB groups (all P < 0.05).Conclusions:This study demonstrated that the function of pDC was unaffected in HBV infection. The enhanced function of pDC and IFN-α2 might involve triggering the immune response from IT to hepatitis active phase in HBV infection. Acute patients mainly presented as down-regulation of the immune response by enhanced IL-10 and TGF-β.

Dynamic Changes of Cytokine Profiles and Virological Markers Associated With HBsAg Loss During Peginterferon Alpha-2a Treatment in HBeAg-Positive Chronic Hepatitis B Patients

“…If patients were given consolidation treatment of interferon for 12-24 weeks after functional cure, it was not easy to relapse ( 10 , 12 , 13 ). We also found that incidence of hepatitis B was positively correlated with IFN-α, and negatively correlated with transforming growth factor-beta (TGF-β) and interleukin- 10 (IL-10) ( 14 , 15 ). Both TGF-β and interferon-gamma (IFN-γ) were found to be associated with efficacy of interferon ( 16 ).…”

“…The presence of HBsAg and HBeAg can damage immune cells, induce production of regulatory T cells, and inhibit the function of immune effector cells ( 14 , 15 , 25 , 26 ). NA treatment cannot effectively reduce viral antigen, so it is difficult to achieve clinical cure ( 7 ).…”

Transforming Growth Factor -β Level&nbsp;Might&nbsp;Be An Independent Factor Related to Occurrence of Chronic Hepatitis B

“…Recovery from HBV infection is dependent on the presence of dendritic cells (DCs), natural killer (NK) cells, CD4 + T lymphocytes cells, and CD8 + T lymphocytes cells, combined with the cytokines secreted by them. The abnormalities of helper T lymphocytes (TH), DC and cytokines in the cellular immunity of patients with CHB are closely related to the pathogenesis and chronicity of hepatitis B [4][5][6] .…”

The Effects of Bushen Jianpi Recipe on the Maturation of Plasmacytoid Dendric Cell to Treat Chronic Hepatitis B&nbsp;

“…In HBV infection condition, pDC is one of the main effector cells in the early antiviral innate immune response [20]. Previous studies have shown that pDC is impaired in CHB patients [21]. CHB patients manifest decreased IFN-I, implying suppressed natural killer (NK) cell and macrophagocyte, which is a reason for HBV immunity escape [8].…”