急性EB病毒感染患儿Toll样受体的变化

Change of Toll-like receptors in children with acute Epstein-barr virus infection

目的探讨Toll样受体（TLRs）信号途径异常活化在急性EB病毒（EBV）感染免疫发病机制中的作用。方法采用病例对照研究方法，选取急性EBV感染患儿15例，传染性单核细胞增多症（IM）患儿18例，同龄健康对照儿童25例，采用反转录-PCR（RT-PCR）及实时荧光定量PCR法检测其外周血单个核细胞TLRs（2、3、7、9）、TLR MyD88-依赖性途径转导分子髓样分化因子88（MyD88）、TNF受体相关因子6（TRAF6）、转化生长因子13激活性激酶1（TAKl）与MyD88-非依赖性途径转导分子B干扰素TIR结构域衔接蛋白（TRIF）、TNF受体相关因子3（TRAF3）、TANK结合激酶l（TBKl）、IL-1β、TNF-α及IFN-α、IFN-βmRNA的表达；应用ELISA法测其血浆IL-12、IFN-γ水平。结果1．急性EBV感染组与IM组TLR2、TLR3、TLR7、TLR9表达均明显高于健康对照组（P均〈0．05），急性EBV感染组与IM组比较差异无统计学意义（P均〉0．05）；TLR信号途径传导分子（MyD88、TRAF6、TAKl、TRIF、TRAF3、TBKl）在急性EBV感染组与IM组表达均较健康对照组显著升高（P均〈0．05）。2．急性EBV感染组与IM组细胞因子IL-1βmRNA、TNF-αmRNA、IFN-αmRNA、IFN-βmRNA表达均较健康对照组显著升高（P均〈0．05），IM组IL-1p、TNF-OL表达显著高于急性EBV感染组（P均〈0．05）。3．急性EBV感染组和IM组血浆IL-12与IFN-γ水平均较健康对照组显著升高（P均〈0．05），IM组升高幅度均较EBV感染组显著（P均〈0．05）。结论TLR2、TLR3、TLR7、TLR9过度活化所致抗病毒反应／炎性反应失衡，可能是急性EBV感染导致体内免疫功能紊乱的原因之-。

Objective To investigate the possible role of Toll-like receptors （TLRs） in immunological pathogenesis of Epstein-barr virus（EBV） infection. Methods Fifteen children with acute EBV infection, 18 children with infectious mononucleosis （IM） , and 25 age-matched healthy children were enrolled in the study. Reverse-transcription polymerase chain reaction and real-time PCR were used to evaluate the levels of TLR2, TLR3, TLRT, TLR9, myeloid differentiation factor 88 （ MyD88 ）, tumor necrosis factor receptor-associated factor 6 （ TRAF6 ）, TGF-β activated kinase 1 （TAK1） ,TIR domain-containing adaptor protein inducing interferon β （TRIF） ,tumor necrosis factor receptor-associated factor 3 （ TRAF3 ）, TBK1, IL-1β, TNF-α, IFN-α and IFN-β mRNA expression in peripheral blood mononuclear cells（PBMC）. The plasma concentrations of cytokines such as IL-12 and interferon gamma （IFN-γ） were determined by enzyme-linked immunosorbent assay. Results 1. Compared with healthy control group, the expression levels of TLR2,TLR3, TLR7, TLR9, MyD88, TRAF6, TAK1, TRIF, TRAF3 and TBK1 mRNA were up-regulated significantly from the children with acute EBV infection and IM （ all P 〈 O. 05 ）, there was no difference between the children with acute EBV infection and IM（al] P〉 0.05 ）. 2. The levels of cytokines expression such as IL-1β, TNF- α, IFN-α and IFN-β in children with acute EBV infection were higher than those of the healthy control group （ a11 P 〈 0.05 ）. 3. The plasma concentrations of IL-12 and IFN-γ were up-regulated （ all P 〈 0.05 ） in children with acute EBV infection. Conclusion Imbalance of antiviral/inflammatory response resulting from the aberrant activation of TLRs may be one of the factors causin~ disturbed immunological function in vivo infected by EBV.