中文摘要：研究采用预防小鼠模型分析了革兰氏阳性增强子基质颗粒（GEM）佐剂的作用机理。结果表明，GEM能够增强口服幽门螺旋杆菌疫苗的效率，促进产生自然免疫。由GEM颗粒和重组抗原CTB-UE组成的疫苗CUE-GEM能够提供免疫小鼠抗幽门螺旋杆菌的保护作用；这种保护作用伴随着胃炎和局部性Th1/Th17 细胞介导的免疫反应。研究结果表明，采用GEM佐剂后，机体自发炎性反应包括中性粒细胞趋化因子CXCL1-2、中性白细胞和抗菌蛋白S100A8和MUC1均显著增加；在所有感染小鼠中S100A8和MUC1与幽门螺杆菌数理呈负相关。采用GEM免疫的小鼠中幽门螺旋杆菌的增殖量降低，这可能是通过自然宿主反应路径募集CD4（+） T细胞和促进S100A8表达引起的。这些结果表明，基于GEM的疫苗可能会影响Th1/Th17免疫，从而触发抗幽门螺旋杆菌感染的自然免疫反应。
外文摘要：Background: Gram-positive enhancer matrix particles (GEM) produced by Lactococcus lactis can enhance vaccine-induced immune response. However, the mechanism under which this adjuvant mounts the efficacy of orally administered vaccines remains unexplored. Materials and Methods: We used a prophylactic mice model to investigate the mechanism of GEM-adjuvanted vaccination. Helicobacter pylori urease-specific antibody response was monitored and detected in murine serum by ELISA. Urease-specific splenic cytokine profile was examined. Gastric inflammatory responses were measured on day 43 or 71 by quantitative real-time PCR, flow cytometry and histology. Results: We found that GEM enhanced the efficiency of oral H. pylori vaccine by promoting innate immunity. The vaccine CUE-GEM composed of GEM particles and recombinant antigen CTB-UE provided protection of immunized mice against H. pylori insult. The protective response was associated with induction of postimmunization gastritis and local Th1/Th17 cell-medicated immune response. We showed that innate inflammatory responses including neutrophil chemokines CXCL1-2, neutrophils, and antimicrobial proteins S100A8 and MUC1 were significantly elevated. Within all infected mice, S100A8 and MUC1 levels were negatively correlated with H. pylori burden. Strikingly, mice receiving GEM also show reduction of colonization, possibly through natural host response pathways to recruit CD4(+) T cells and promote S100A8 expression. Conclusions: These findings suggest that GEM-based vaccine may impact Th1/Th17 immunity to orchestrate innate immune response against H. pylori infection.
外文关键词：Helicobacter pylori, innate immunity, Lactococcus lactis
作者：Liu, W; Tan, ZL; Liu, H; Zeng, ZQ; Luo, SH; Yang, HM; Zheng, LF; Xi, T; Xing, YY
作者单位：中国药科大学
期刊名称：HELICOBACTER
期刊影响因子：3.6
出版年份：2017
出版刊次：10
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