Overexpression of Toll-like receptor 2/4 on monocytes modulates the activities of CD4(+)CD25(+) regulatory T cells in chronic hepatitis B virus infection

Virology. 2010 Feb 5;397(1):34-42. doi: 10.1016/j.virol.2009.11.007. Epub 2009 Nov 27.

Abstract

The significance of TLR expression and Tregs in HBV infection has not been clearly described. In this report, flow cytometry was performed to assess TLR2/4 expression on monocytes and circulating CD4(+)CD25(+)CD127(low/-) Tregs frequency of 16 acute hepatitis B (AHB), 42 chronic hepatitis B (CHB), 22 asymptomatic HBV carriers (AsC), and 20 normal controls (NC). We found that TLR2 and TLR4 were overexpressed on CD14(+) monocytes in HBV-infected patients as compared with NCs. Upregulation of TLR2 in NCs and TLR4 in CHBs was observed following HBeAg incubation. However, TLR2 and TLR4 expression decreased after HBcAg stimulation. The difference in the proportion of Tregs between NCs and CHBs was significant. Both Pam3Csk4 (TLR2 agonist)- and lipopolysaccharide (TLR4 agonist)-activated CD4(+)CD25(+) Tregs showed enhanced suppression function in CHBs. These results suggest that overexpression of TLR2 and TLR4 may modulate the suppressive function of Tregs, which contribute to the immunotolerance of chronic HBV infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • CD4 Antigens / analysis
  • Female
  • Flow Cytometry / methods
  • Hepatitis B virus / immunology
  • Hepatitis B, Chronic / immunology*
  • Humans
  • Interleukin-2 Receptor alpha Subunit / analysis
  • Interleukin-7 Receptor alpha Subunit / analysis
  • Lipopolysaccharide Receptors / analysis
  • Male
  • Monocytes / chemistry
  • Monocytes / immunology*
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocytes, Regulatory / chemistry
  • T-Lymphocytes, Regulatory / immunology*
  • Toll-Like Receptor 2 / biosynthesis*
  • Toll-Like Receptor 4 / biosynthesis*
  • Young Adult

Substances

  • CD4 Antigens
  • IL2RA protein, human
  • Interleukin-2 Receptor alpha Subunit
  • Interleukin-7 Receptor alpha Subunit
  • Lipopolysaccharide Receptors
  • TLR2 protein, human
  • TLR4 protein, human
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4