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Overexpression of Toll-like receptor 2/4 on monocytes modulates the activities of CD4CD25 regulatory T cells in chronic hepatitis B virus infection
Authors:Ye Zhang  Jian-Qi Lian  Chang-Xing Huang  Xin Wei  Hai-Tao Yu  Xiao-Qin Wang  Xin-Hong Li  Ping-Zhong Wang  Xue-Fan Bai
Affiliation:a Center of Infectious Diseases, Tangdu Hospital, Fourth Military Medical University, 1 Xin Si Road, Ba Qiao District, Xi'an 710038, Shaanxi Province, China
b Department of Pathology, Yale University School of Medicine, New Haven, CT 06510, USA
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+CD127low/− 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.
Keywords:Hepatitis B virus   Toll-like receptors   Regulatory T cells   innate immune   immunoregulation
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