College of Animal Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, China.
Institute of Materia Medica, Zhejiang Academy of Medical Sciences, Hangzhou 310013, China.
Int J Biol Macromol. 2020 Aug 1;156:1202-1216. doi: 10.1016/j.ijbiomac.2019.11.158. Epub 2019 Nov 21.
The innate immune mechanisms by which adjuvants enhance the potency and protection of vaccine remain at cellular level, but the molecular mechanisms, especially in vivo, are ill-identified. Actinidia eriantha polysaccharide (AEPS) is a potent adjuvant with dual Th1 and Th2 potentiating activity, while Alum elicits a strict Th2 response. The current experiments were designed to compare the innate immune responses in the peritoneal cavity of mice induced by two adjuvants and explore their molecular mechanisms using gene expression microarray including long noncoding RNAs (lncRNAs). AEPS induced the recruitment of monocytes, neutrophils and dendritic cells. However, Alum recruited neutrophils and eosinophils. AEPS and Alum specifically induced the differential expression of 546 and 922 genes in peritoneal cells, respectively. AEPS induced higher mRNA expression of CCL2, CCL3, CCL4, CCL7, CXCL2, CXCL3, CXCL5, CXCL10, IL-12β, and IL-23α in immune effector process, while Alum tended to Th17 response mRNAs such as IL-7A, IL-17F and IL-17RA. Furthermore, a robust adjuvant-specific expression pattern of lncRNAs was found in above mentioned biological processes, suggesting the involvement of lncRNAs in immune responses induced by AEPS and Alum. This study led to a better understanding of different molecular mechanisms of adjuvants and benefited the rational design of effective vaccines.
佐剂增强疫苗效力和保护作用的先天免疫机制仍处于细胞水平,但分子机制,特别是在体内,仍不清楚。猕猴桃多糖(AEPS)是一种具有双重 Th1 和 Th2 增强活性的有效佐剂,而明矾则引发严格的 Th2 反应。本实验旨在比较两种佐剂诱导小鼠腹腔内先天免疫反应,并利用包括长链非编码 RNA(lncRNA)在内的基因表达微阵列探索其分子机制。AEPS 诱导单核细胞、中性粒细胞和树突状细胞的募集。然而,明矾招募了中性粒细胞和嗜酸性粒细胞。AEPS 和明矾分别特异性诱导腹腔细胞中 546 和 922 个基因的差异表达。AEPS 诱导 CCL2、CCL3、CCL4、CCL7、CXCL2、CXCL3、CXCL5、CXCL10、IL-12β 和 IL-23α 在免疫效应过程中的 mRNA 表达水平更高,而明矾则倾向于 Th17 反应的 mRNAs,如 IL-7A、IL-17F 和 IL-17RA。此外,在上述生物学过程中发现了 lncRNAs 的强大佐剂特异性表达模式,表明 lncRNAs 参与了 AEPS 和明矾诱导的免疫反应。本研究加深了对佐剂不同分子机制的理解,有利于有效疫苗的合理设计。