疟疾感染过程中Th17对DCs功能的调控作用及机制研究

Regulation and Mechanism effects of Th17 on DCs Function in Malaria

目的探讨辅助性T细胞17(Th17)在疟疾的发生发展过程中对DCs功能的调控作用及机制。方法构建P.y17XL感染的BABL/c小鼠模型和Th17消除的疟疾感染小鼠模型,记录红细胞感染率和生存率。于感染后第0、3和5 d,分别进行脾细胞悬液的制备,FACS检测脾脏中DCs亚群数量、表面分子CD86、MHC-II和CD80的表达水平及分泌IL-10、IL-12的DCs数量变化。结果相比较正常感染组小鼠,P.y17XL感染小鼠于感染后3 d Th17约占CD4^(+)T细胞的(16.7±3.3)%,感染后5 d达峰值,约占CD4^(+)T细胞的(19.6±2.6)%,均显著高于正常对照组(2.4±0.3)%。IL-17A消除组小鼠CD4^(+)T细胞中Th17的比例均低于对照组,第3 d和第5 d分别减少86.2%和84.1%。Th17消除组小鼠在感染后第3 d,DCs亚群、CD86、MHC-II和CD80表面分子的表达都有较显著的增加;在感染后第5 d,DCs亚群、CD80和MHC-II表面分子的表达都有较显著的减少;在感染后第5 d分泌IL-12和IL-10的DCs数量百分比显著增加,是同天感染鼠的5.8和2.5倍。结论P.y17XL感染早期,Th17细胞能有效的短期抑制DCs的免疫功能,后DCs功能迅速恢复;可能与Th17调控DCs的细胞因子分泌模式、亚群以及表型等密切相关。

Objective To investigate the regulatory effect and mechanism of helper T cell 17(Th17)on DCs function in the occurrence and development of malaria.Methods The BABL/c mouse model infected with P.y17XL and the malaria infection mouse model eliminated by Th17 were constructed to record the erythrocyte infection rate and survival rate.At 0,3 and 5 days after infection,spleen cell suspension was prepared.The number of DCs subsets,the expression levels of surface molecules CD86,MHC-II and CD80,and the number of DCs secreting IL-10 and IL-12 were detected by FACS.Results Compared with the normal infection group,Th17 accounted for(16.7±3.3)%of CD4^(+)T cells in P.y17XL infected mice at 3 d after infection,and reached the peak at 5 d after infection,accounting for(19.6±2.6)%of CD4^(+)T cells,which were significantly higher than those in the normal control group(2.4±0.3)%.The proportion of Th17 cells in CD4^(+)T cells in IL-17A-eliminated group was lower than that in control group,and decreased by 86.2%and 84.1%on day 3 and 5,respectively.The expression of DCs subsets,CD86,MHC-II and CD80 surface molecules in Th17 elimination group increased significantly on the 3rd day after infection.On day 5 after infection,the expression of DCs subsets,CD80 and MHC-II surface molecules decreased significantly.The percentage of DCs secreting IL-12 and IL-10 on the 5th day after infection was significantly increased,5.8 and 2.5 times that of the infected rats on the same day.Conclusion In the early stage of P.y17XL infection,Th17 cells can effectively inhibit the immune function of DCs in the short term,and then the DCs function recovers rapidly.It may be closely related to Th17 regulating cytokine secretion patterns,subsets and phenotypes of DCs.