Mechanisms of Mixed Th1/Th2 Responses in Mice Induced by Albizia julibrissin Saponin Active Fraction by in Silico Analysis
Mechanisms of Mixed Th1/Th2 Responses in Mice Induced by Albizia julibrissin Saponin Active Fraction by in Silico Analysis
复制标题
计算机模拟分析合欢皂苷活性组分诱导小鼠混合 Th1/Th2 反应的机制
DOI：
10.3390/vaccines8010048
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发表时间：
2020-03-01
期刊：
影响因子：
7.8
通讯作者：
Sun, Hongxiang
中科院分区：
文献类型：
--
作者：
Du, Jing;Jin, Junjie;Sun, Hongxiang
合欢皂苷活性组分（AJSAF）是一种理想的佐剂候选物，可提高抗原特异性细胞免疫和体液免疫应答，并可增强Th 1/Th 2混合免疫应答，但其作用机制尚不清楚。以纽卡斯尔病毒重组流感疫苗（rL-H5）和AJSAF在同一腿（AJSAF+rL-H5）或不同腿（AJSAF/rL-H5）免疫小鼠，研究AJSAF的主要作用特点。AJSAF对rL-H5的佐剂活性严格依赖于它们的空间共定位。AJSAF+rL-H5组血清H5抗原特异性IgG、IgG 1、IgG 2a和IgG 2b抗体滴度均显著高于AJSAF/rL-H5组。采用基因芯片和双向差异凝胶电泳结合基质辅助激光解吸电离飞行时间质谱技术，对AJSAF诱导的小鼠Th 1或Th 2选择性免疫应答的转录组学和蛋白质组学特征进行了研究。与单独的rL-H5相比，AJSAF/rL-H5比AJSAF+rL-H5诱导更多的差异表达基因（DEG），而AJSAF+rL-H5上调Th 1（T-bet、IFN-γ、TNF-α、IL-12β和IL-12 R β1）和Th 2（IL-10和AICDA）免疫应答基因的更高mRNA表达。中性粒细胞反应及其衍生的S100 A8和S100 A9可能参与AJSAF介导的Th 1反应。同时，AJSAF可能通过改善局部天然免疫微环境而诱导获得性免疫应答。这些发现扩展了目前关于皂苷类佐剂作用机制的知识，并为佐剂如何塑造适应性免疫反应提供了新的见解。
The purified active fraction of Albizia julibrissin saponin (AJSAF) is an ideal adjuvant candidate that improves antigen-specific both cellular and humoral immune responses and elicits mixed Th1/Th2 responses, but its mechanisms remain unclear. The key features of action of AJSAF were investigated in mice immunized with Newcastle disease virus-based recombinant influenza vaccine (rL-H5) and AJSAF at the same leg (AJSAF+rL-H5) or different legs (AJSAF/rL-H5). The adjuvant activity of AJSAF on rL-H5 is strictly dependent on their spatial colocalization. Serum H5 antigen (H5Ag)-specific IgG, IgG1, IgG2a, and IgG2b antibody titers in AJSAF+rL-H5 group were significantly higher than those in AJSAF/rL-H5 group. The mechanisms of selectivity of Th1 or Th2 in mice induced by AJSAF was explored by the transcriptomic and proteomic profiles of H5Ag-stimulated splenocytes from the immunized mice using gene microarray and two-dimensional difference gel electrophoresis coupled with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Compared to rL-H5 alone, AJSAF/rL-H5 induced more differentially expressed genes (DEGs) than AJSAF+rL-H5, whereas AJSAF+rL-H5 upregulated higher mRNA expression of Th1 (T-bet, IFN-γ, TNF-α, IL-12β, and IL-12Rβ1) and Th2 (IL-10 and AICDA) immune response genes. The neutrophil response and its derived S100A8 and S100A9 might be involved in the AJSAF-mediated Th1 response. Meanwhile, AJSAF might induce the adaptive immune responses by improving a local innate immune microenvironment. These findings expanded the current knowledge on the mechanisms of action of saponin-based adjuvants, and provided new insights into how adjuvants shape adaptive immune responses.