ABSTRACT
<p><b>OBJECTIVE</b>To investigate the changes in circulating plasmacytoid dendritic cells (pDCs) in patients with chronic hepatitis B (CHB) during the course of treatment with pegylated-interferon alfa-2s (peg-IFNa-2a) and to determine the correlations with therapeutic response.</p><p><b>METHODS</b>Forty-one patients with CHB who were receiving peg-IFNa-2a antiviral treatment for 48 weeks were enrolled in the study.Expression of the Toll-like receptor 9 (TLR9) on and frequency and functionality of the pDCs were analyzed at treatment weeks 0, 2, 12, 24, 36 and 48.</p><p><b>RESULTS</b>All patients exhibited an initially rapid decrease in the numbers of circulating pDCs and showed CpG-induced endogenous IFNa production within the first 2 weeks of treatment.Subsequently, all responders displayed a continuous increase in pDC numbers as well as functionality, both of which peaked around week 12 of treatment; in addition, these treatment responses were accompanied by significantly increased levels of type 1 T helper cytokines (P less than 0.05), which did not occur in the non-responders.</p><p><b>CONCLUSION</b>pDCs are involved in the initial therapeutic immune response stimulated by peg-IFNa-2a treatment.Recovery of blood pDC number and functionality may represent a predictor of favorable response to peg-IFNa-2a antiviral treatment in patients with CHB.</p>
Subject(s)
Humans , Antiviral Agents , Dendritic Cells , Hepatitis B, Chronic , Interferon-alpha , Polyethylene Glycols , Recombinant Proteins , Toll-Like Receptor 9 , Treatment OutcomeABSTRACT
Objective To investigate the expression and function of retinoic acid-inducible gene Ⅰ(RIG-Ⅰ) in monocyte-derived dendritic cells (MoDC) at different stages of hepatitis B virus(HBV)infection and to explore the role of RIG-Ⅰ in the disease progression after HBV infection. Methods Peripheral blood samples were collected from 28 hepatitis B virus-infected persons, including 21 cases of chronic hepatitis B (CHB) and 7 of acute hepatitis B (AHB). Eighteen healthy subjects were recruited as controls. Purified CD14~+ monocytes were isolated by CD14 microbeads. MoDCs were induced from CD14~+ monocytes with granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin (IL)-4 for 7 days, and then were infected with vesicular stomatitis virus (VSV) to stimulate RIG-Ⅰ expression. The mRNA expression levels of RIG-Ⅰ, interferon (IFN )-promoter stimulating factor-1 (IPS-1) and IFN-β at 16 hours and 24 hours after infection with VSV were measured by real-time quantitative polymerase chain reaction (PCR). Data with normal distribution were tested by analysis of variance. Continuous variables between groups were compared using Mann-Whitney U test. Comparison among multiple groups was done by Kruskal-Wallis test. Results The expression levels of RIG-Ⅰ in MoDCs from CHB patients were significantly lower than those in AHB patients and healthy controls at 16 hours (2.44±2.03, 19. 54±3. 15, 21. 48±8. 39, respectively; F=7.451,P=0.002) and 24 hours (2. 68±2. 93, 10. 31 ±3. 88, 14. 01 ±5. 04, respectively, F = 7. 908, P = 0. 001)following VSV stimulation. The IPS-1 levels in both CHB patients and AHB patients were higher than those in healthy controls at 16 hours (2. 05±l. 08, 1. 99±1. 56, 0. 60±0. 31, respectively) F=7.246,P =0.003) and 24 hours (2. 27±2. 16, 3.24 ± 1.21, 1. 08±0. 73, respectively; F= 13. 598, P = 0. 001).Furthermore, the IFN-β expression levels were significantly lower in CHB patients compared to AHB patients and healthy controls at 16 hours and 24 hours after VSV stimulation. Conclusions The expressions of RIG-Ⅰ and IPS-1 in MoDC are abnormal in HBV infected persons, which indicates that RIG-Ⅰ signaling pathway might be blocked by HBV. The impaired function of MoDC may play a role in HBV infection and chronicity.
ABSTRACT
Objective To elucidate the roles of TANK-binding kinase-1(TBKl)in hepatitis B virus (HBV)infection induced interferon antiviral immunity.Methods Peripheral blood monocytes were separated by CD14 magnetic microbeads from healthy volunteers(HV)and chronic hepatitis B(CHB)patients.Purified mDCs were induced and proliferated in the culture medium with human granulocyte-macrophage concentration of 25 mg/L were stimulated.The mRNA expressions of TBK1,interferon regulatory factor (IRF)3 and interferon(IFN)-βwere quantified by real time polymerase chain reaction(PCR).The levels of IFN-β in supernatants were determined by enzyme-linked immunosorbent assay(ELISA).Reslllts The mRNA levels of TBK1,IRF3 and IFN-β did not change significantly at 0,12,24 and 48 h after the significantly at 0, 12, 24 and 48 h in CHB group, whereas, it was significantly up-regulated at 12 h in HV group. Conclusions Our results suggest that there may be some disorders in host antiviral signal transduction pathways downstream the binding between ligands and receptors on mDC surface. The insufficient IFN-β expression after HBV infection may result in persistent chronic infection.