登革热患者外周血单个核细胞中模式识别受体相关基因表达水平的初步研究

Expression of genes associated with pattern recognition receptors in peripheral blood mononuclear cells from patients with dengue fever

目的探讨固有免疫模式识别受体（PRRs）包括Toll样受体（TLRs）、维甲酸诱导基因I样受体（RLRs）和核苷酸结合寡聚化结构域样受体（NLRs）及其信号通路在登革热致病和免疫过程中的作用。方法收集登革热患者病程中3个不同时间点的抗凝外周血标本，用密度梯度离心法分离外周血单个核细胞（PBMC），提取细胞RNA，用聚合酶链反应芯片（PCR array）检测基因表达水平。结果84个基因中部分受体分子、信号分子和效应分子基因在登革热患者PBMC中表达异常，与健康对照相比，主要表现为表达上调，尤其在登革热发病早期，之后随病情恢复．基因表达水平逐渐趋于正常；其中TLRs家族中TLR7和TLR8受体基因表达水平显著升高，而TLR3和TLR9基因表达没有明显变化；RLRs家族中3个受体分子RIG—I、MDA5和LGP2基因表达水平均显著上调，NLRs家族中OAS2和NOD2受体基因表达也表现为上调。结论PRRs介导的信号通路在登革热致病及免疫过程中起重要作用。

Objective To investigate the roles of pattern recognition receptors （PRRs） including Toll-like receptors （TLRs）, retinoic acid-inducible gene I -like receptors （RLRs） and nucleotide binding oligumerization domain-like receptors （NLRs） in the pathogenesis of dengue fever （DF） and the induction of immune responses to dengue virus. Methods Blood samples were collected from patients with DF at three different time points to isolate peripheral blood mononuclear cells （PBMCs） by density gradient centrifugation. Then PBMCs were used to extract ribonucleic acid （RNA）. Expression of genes was detected by polymerase chain reaction （PCR） array. Results Expression of genes relating to PRRs signaling pathways in DF patients increased significantly in the early stage of the disease as compared with those in healthy con- trols, but decreased gradually during the recovery period. Expression of genes encoding TLR7 and TLR8 was enhanced at the early stage of DF. No significant changes in the expression of TLR3 and TLR9 genes were observed during the course of the disease. The genes encoding RIG- I , MDA5 and LGP2 of RLRs family as well as NOD2 and OAS2 of NLRs family were all up-regulated. Conclusion Signaling pathways mediated by PRRs including TLRT/8, RIG- I , MDA5 and so on play an important role in the pathogenesis of DF and the induction of immune responses to dengue virus.