The expression and function of retinoic acid-inducible gene Ⅰ in monocyte-derived dendritic cells in patients with hepatitis B virus infection / 中华传染病杂志

ABSTRACT

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.