Toll样受体2介导的Th17细胞活化在HBV感染中的作用  

Toll- like receptor 2 drives Th17 cell activation in inflammatory response to hepatitis B virus infection

作　　者：赵荣荣[1] 杨晓飞[1] 董杰[1] 黄长形[1] 张野[1] 连建奇[1] 

机构地区：[1]第四军医大学唐都医院全军感染病诊疗中心,西安710038

出　　处：《临床肝胆病杂志》2014年第9期877-881,共5页Journal of Clinical Hepatology

基　　金：陕西省自然科学基础研究计划项目(2012JQ4023);国家"十二五"传染病重大专项(2012ZX10002-007-001-006)

摘　　要：目的探讨乙型肝炎患者外周血单个核细胞(PBMC)中Toll样受体2(TLR2)与Th17细胞的相关性,为阐述HBV感染诱导炎症应答机制提供理论和实验依据。方法选取2012年7月-2013年7月唐都医院感染科门诊和住院的34例乙型肝炎初治患者,其中24例慢性乙型肝炎和10例急性乙型肝炎;另外选取健康对照者10例,分离PBMC,利用HBV C基因型Envelope区肽段(特异性)或佛波酯联合伊屋诺霉素(非特异性)刺激,流式细胞术检测TLR2表达及Th17细胞百分比。进一步用TLR2的激动剂刺激PBMC,检测Th17细胞变化情况。组间比较采用Kruskal-Wallis H检验。结果在非特异性刺激条件下,Th17细胞在慢性乙型肝炎患者体内的百分比(4.08±1.78)%显著高于急性乙型肝炎患者(1.85±1.28)%及健康对照者(2.09±0.53)%(P=0.000 9、0.000 4),而TLR2+及IL-17A+TLR2+的表达在急、慢性乙型肝炎患者与健康人外周血中差异均无统计学意义(P均>0.05)。在特异性刺激条件下Th17及TLR2的表达在慢性乙型肝炎患者体内的表达显著高于急性乙型肝炎组[(5.45±1.61)%vs(3.20±1.13)%;(5.19±3.18)%vs(1.88±1.30)%],差异具有统计学意义(P=0.000 6、0.000 6)。加入TLR2激动剂后急、慢性乙型肝炎患者体内Th17细胞的比例均显著升高,但在急性乙型肝炎患者中,刺激前后差异无统计学意义(P>0.05)。结论 TLR2可以直接影响Th17细胞的应答,从而促进乙型肝炎中炎症应答反应。Objective To investigate the relationship between Toll- like receptor 2（ TLR2） in peripheral blood mononuclear cells（ PBMCs） and T helper 17（ Th17） cells among hepatitis B patients and to provide a theoretical and experimental basis for the study on the mechanism of inflammatory response to hepatitis B virus（ HBV） infection. Methods Thirty- four previously untreated patients with hepatitis B（ 24 cases of chronic hepatitis B and 10 cases of acute hepatitis B） who visited or were hospitalized in the Center of Infectious Diseases,Tangdu Hospital,from July 2012 to July 2013,as well as ten healthy controls,were enrolled in this study. PBMCs were isolated and stimulated by HBV（ genotype C） envelope peptides（ specific） or propylene glycol monomethyl ether acetate（ PMA） plus ionomycin（ nonspecific）. Flow cytometry was performed to measure the expression of TLR2 and the percentage of Th17 cells. PBMCs were further stimulated by TLR2 agonist Pam3Csk4,and the changes in percentage of Th17 cells were evaluated. Comparison between groups was made by Kruskal-Wallis H test. Results When stimulated by PMA plus ionomycin,patients with chronic hepatitis B had a significantly higher percentage of Th17 cells than patients with acute hepatitis B and healthy controls [（ 4. 08 ± 1. 78） % vs（ 1. 85 ± 1. 28） %,P = 0. 0009;（ 4. 08 ±1. 78） % vs（ 2. 09 ± 0. 53） %,P = 0. 0004],while the percentages of TLR2＋and IL- 17A＋TLR2＋T cells in peripheral blood CD3＋CD4＋T cells showed no significant differences between patients with acute hepatitis B,patients with chronic hepatitis B,and healthy controls（ P〉0. 05 for all）. When stimulated by HBV envelope peptides,patients with chronic hepatitis B had significantly higher percentages of IL- 17A＋T cells and TLR2＋T cells than patients with acute hepatitis B [（ 5. 45 ± 1. 61） % vs（ 3. 20 ± 1. 13） %,P = 0. 0006;（ 5. 19± 3. 18） % vs（ 1. 88 ± 1. 30） %,P = 0. 0006]. After the addition of Pam3Csk4,patients with chroni

关 键 词：肝炎 乙型 TH17细胞 TOLL样受体2 白细胞介素17 

分 类 号：R512.62[医药卫生—内科学]