Relationship between expression of toll-like receptors 2/4 in dendritic cells and chronic hepatitis B virus infection

Int J Clin Exp Pathol. 2014 Aug 15;7(9):6048-55. eCollection 2014.

Abstract

Objective: This study is to explore the relationship between the chronic hepatitis B virus (HBV) infection and the expressions of toll-like receptor 2/4 (TLR2/4) in peripheral blood dendritic cells (DCs), to find out the immunological significance of TLR2/4 in HBV progression.

Methods: Patients had been divided into the HBV, HBV-related liver cirrhosis (HBV-LC), and HBV-related hepatocellular carcinoma (HBV-HCC) groups. Healthy individuals served as normal controls (NC). Flow cytometry was used to determine the percentage of DCs in peripheral blood, and the expression of TLR2/4 in DCs as well as the expression of HBeAg. Real-time quantitative PCR was performed to measure the content of HBV-DNA.

Results: The percentages of DCs in peripheral blood exhibited a slightly decreasing trend, without statistical significances, along with the disease severity in HBV patients (9.40 ± 2.05%, 7.11 ± 3.82%, 6.51 ± 4.38% and 6.00 ± 4.73% for the groups of NC, HBV, HBV-LC, and HBV-HCC, respectively). The expression of TLR2 was significantly increased in the disease progression, with the TLR2 expression rates of 2.60 ± 1.70%, 2.67 ± 2.89%, 3.53 ± 3.41% and 5.11 ± 4.93 for NC, HBV, HBV-LC, HBV-HCC, respectively. Similar results were found for TLR4 (expression rates: 45.34 ± 4.46%, 53.94 ± 5.21%, 65.16 ± 5.92% and 75.54 ± 6.12%), which was positively correlated with TLR2. Furthermore, the HBeAg level was increased, while the amount of HBV-DNA exhibited a declining trend, along with the disease severity. Correlation analysis revealed that the expression of HBeAg was positively correlated with TLR2.

Conclusions: The elevated expressions of TLR2/4 on DC cell surfaces in peripheral blood may synergistically promote the disease progression of chronic HBV infection.

Keywords: Hepatitis B virus; chronic infection; dendritic cells; toll-like receptors 2/4.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Biomarkers / blood
  • Carcinoma, Hepatocellular / blood
  • Carcinoma, Hepatocellular / diagnosis
  • Carcinoma, Hepatocellular / immunology*
  • Carcinoma, Hepatocellular / virology
  • Case-Control Studies
  • Child
  • DNA, Viral / blood
  • Dendritic Cells / immunology*
  • Dendritic Cells / virology
  • Disease Progression
  • Female
  • Flow Cytometry
  • Hepatitis B e Antigens / blood
  • Hepatitis B virus / genetics
  • Hepatitis B virus / immunology
  • Hepatitis B, Chronic / blood
  • Hepatitis B, Chronic / complications
  • Hepatitis B, Chronic / diagnosis
  • Hepatitis B, Chronic / immunology*
  • Humans
  • Liver Cirrhosis / blood
  • Liver Cirrhosis / diagnosis
  • Liver Cirrhosis / immunology*
  • Liver Cirrhosis / virology
  • Liver Neoplasms / blood
  • Liver Neoplasms / diagnosis
  • Liver Neoplasms / immunology*
  • Liver Neoplasms / virology
  • Male
  • Middle Aged
  • Prognosis
  • Real-Time Polymerase Chain Reaction
  • Severity of Illness Index
  • Toll-Like Receptor 2 / blood*
  • Toll-Like Receptor 4 / blood*
  • Young Adult

Substances

  • Biomarkers
  • DNA, Viral
  • Hepatitis B e Antigens
  • TLR2 protein, human
  • TLR4 protein, human
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4