阻断Notch信号对疫苗增强性免疫病理的作用  

The role of blocking Notch signaling in enhancing the immunopathology of the FI-RSV vaccine

作　　者：李宏勇[1] 韩艳娟[1] 田新利[1] 林玲辉[1] 刘建勋[1] 曾瑞红[2] 

机构地区：[1]邢台医学高等专科学校,河北邢台054000 [2]河北医科大学免疫学教研室

出　　处：《中国病原生物学杂志》2017年第3期214-218,共5页Journal of Pathogen Biology

基　　金：河北省自然科学基金项目(No.H2016206473)

摘　　要：目的探讨阻断Notch信号对FI-RSV疫苗增强性免疫病理的调节作用。方法制备加入佐剂Al(OH)3的FI-RSV疫苗,肌注免疫C57BL/6小鼠2次,检测抗体;攻毒后,检测各组体重变化,并作肺组织切片及染色检查和细胞因子转录表达检测。结果免疫前各组血清IgG抗体水平无显著差异;免疫后,FI-RSV+Al(OH)_3组体重下降显著;病理切片PAS染色显示FI-RSV+Al(OH)_3和FI-RSV+Al(OH)_3+L-685,458组的粘液分泌均较明显,病理切片HE染色显示FI-RSV+Al(OH)_3和FI-RSV+Al(OH)_3+L-685,458组肺部均显示大量炎症细胞浸润,炎症反应较强,FI-RSV+Al(OH)_3组炎症反应倾向于肺泡壁,FI-RSV+Al(OH)_3+L-685,458组炎症反应倾向于气管壁和血管周;FIRSV+Al(OH)_3组肺组织RSV-N基因的表达量与FI-RSV+Al(OH)_3+L-685,458组比较差异无统计学意义(P>0.05),FI-RSV+Al(OH)_3组的IFN-γ、TNF-α、T-bet、IL-17、ROR-γt基因的表达量显著高于其他两组(P<0.05),FIRSV+Al(OH)_3+L-685,458组IL-4、IL-5、GATA-3基因的表达量显著高于其他两组(P<0.05)。结论 Al(OH)_3单独作为佐剂比添加L-685,458诱发Th1及Th17型优势应答和以肺泡壁反应为主的炎症反应强;Notch信号阻断后诱发的Th2型优势应答及以气管壁和血管周反应的炎症反应更强。Objective To study the role and regulation of Notch signaling in enhancing the immunopathology of the FIRSV vaccine. Methods AI（OH）a was added to the FI-RSV vaccine and C57B1/6 mice were intramuscularly immunized twice. Antibodies were detected. After a challenge with RSV, changes in body weight were detected, lung tissue was sectioned, and the transcription of various cytokines was detected. Results The IgG antibody titer did not differ significantly in the immunized groups. The ratio of IgG1/IgG2a in mice given FI-RSV＋Al（OH）3＋L-685,458 was higher than that in mice given FI-RSV＋ Al（OH）3. The weight of mice given FI-RSV＋ Al（OH）3 decreased most after a challenge with RSV. Abundant secretion of mucus was evident in mice given FI-RSVq-AI（OH）a and mice given FI-RSV- Al （OH）3＋L 685,458. After a challenge with RSV, infiltration of inflammatory cells, marked thickening of the alveolar walls, and destruction of bronchial walls and blood vessels were observed in mice given FI-RSV＋AI（OH）3and mice given FI-RSV＋ AI（OH） 3＋ L-685,458. The level of RSV-N expression in mice given FI-RSV＋ Al （OH） 3 ＋ L-685,458 and in mice given FI RSV＋Al（OH）3 did not differ significantly. The level of expression of IFN-γ, TNF-α, IL-17, ROR-γt, and T-bet mRNA in mice given FI-RSV＋Al（OH）3 was higher than that in other groups （P〈0.05）. The level of expres sion of IL-4, IL-5, and GATA 3 mRNA in mice given FI-RSV＋Al（OH）3 ＋L-685,458 was higher than that in the other groups （P〈0.05）. Conclusions A predominantly Th1 and Th17 response was induced when AI（OH）3 alone was used as an adjuvant. A strong inflammatory response occurred in the alveolar walls. After Notch signaling was blocked, a pre dominantly Th2 response was induced. A strong inflammatory response occurred around the bronchi.

关 键 词：呼吸道合胞病毒 NOTCH信号 佐剂 疫苗 

分 类 号：R373.1[医药卫生—病原生物学]