Overexpression of Toll-like receptor 2/4 on monocytes modulates the activities of CD4(+)CD25(+) regulatory T cells in chronic hepatitis B virus infection.
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.
Zhang
Ye
Y
Center of Infectious Diseases, Tangdu Hospital, Fourth Military Medical University, 1 Xin Si Road, Ba Qiao District, Xi'an 710038, Shaanxi Province, China.
Lian
Jian-Qi
JQ
Huang
Chang-Xing
CX
Wang
Jiu-Ping
JP
Wei
Xin
X
Nan
Xue-Ping
XP
Yu
Hai-Tao
HT
Jiang
Li-Li
LL
Wang
Xiao-Qin
XQ
Zhuang
Yan
Y
Li
Xin-Hong
XH
Li
Yu
Y
Wang
Ping-Zhong
PZ
Robek
Michael D
MD
Bai
Xue-Fan
XF
D000328:Adult; D015704:CD4 Antigens / Q000032:analysis; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D006515:Hepatitis B virus / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000276:immunology*; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis; D053699:Interleukin-7 Receptor alpha Subunit / Q000032:analysis; D018950:Lipopolysaccharide Receptors / Q000032:analysis; D008297:Male; D009000:Monocytes / Q000737:chemistry / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000737:chemistry / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000096:biosynthesis*; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis*; D055815:Young Adult
D015704:CD4 Antigens; C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit; D053699:Interleukin-7 Receptor alpha Subunit; D018950:Lipopolysaccharide Receptors; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4