Co-expression network analysis identifies innate immune signatures for Albizia julibrissin saponin active fraction-adjuvanted avian influenza vaccine
Co-expression network analysis identifies innate immune signatures for Albizia julibrissin saponin active fraction-adjuvanted avian influenza vaccine
复制标题
共表达网络分析鉴定了合欢皂苷活性组分佐剂禽流感疫苗的先天免疫特征
DOI：
10.1016/j.intimp.2021.107417
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发表时间：
2021-02-04
影响因子：
5.6
通讯作者：
Sun, Hongxiang
中科院分区：
文献类型：
--
作者：
Du, Jing;Sun, Hongxiang
合欢皂苷活性组分（AJSAF）是一种很有前途的佐剂候选物，但其先天免疫应答机制尚不清楚。在这里，将AJSAF单独或与卵清蛋白和禽流感疫苗（rL-H5）联合注射的小鼠的股四头肌进行基因芯片检测。利用加权基因共表达网络分析（WGCNA）和基因集富集分析（GSEA）对具有胞内枢纽基因的抗原和ajaf相关模块进行鉴定和功能分析。AJSAF在注射部位诱导早期先天免疫反应，以细胞因子产生和中性粒细胞募集为特征。AJSAF主要诱导了“Th1免疫应答”和“中性粒细胞”基因CCL2、CXCL1、CXCL5、IL-1 β、IL-6、IL-33、S100A8和S100A9的表达，而rL-H5则负富集了这两个基因集。ajsaf特异性长链非编码rna MIRT1和MIRT2可作为炎症介质，而功能未知的TINCR与免疫应答基因CCL2、CCL4、CCL7、CSF3、CXCL5、IL-33、S100A8和S100A9共表达。最后，提出了AJSAF佐剂作用的先天免疫分子机制及其潜在特征。这些发现扩大了目前对基于皂苷的佐剂的作用机制的认识。
Albizia julibrissin saponin active fraction (AJSAF) is a promising adjuvant candidate, but its innate immune response mechanisms remain unclear. Here, the quadriceps muscles from the mice injected intramuscularly with AJSAF alone or in combination with ovalbumin and avian influenza vaccine (rL-H5) were subjected to gene microarray. Antigen-and AJSAF-related modules with intramodular hub genes were identified and functionally analyzed using weighted gene co-expression network analysis (WGCNA) and gene set enrichment analysis (GSEA). AJSAF induced early innate immune responses at the injection site, characterized by cytokine production and neutrophil recruitment. AJSAF mainly elicited the expression of "Th1 immune response" and "Neutrophils" genes such as CCL2, CXCL1, CXCL5, IL-1 beta, IL-6, IL-33, S100A8, and S100A9, whereas these two gene sets were negatively enriched for rL-H5. AJSAF-specific long noncoding RNAs MIRT1 and MIRT2 could function as inflammatory mediators, whereas function unknown TINCR was co-expressed with immune response genes including CCL2, CCL4, CCL7, CSF3, CXCL5, IL-33, S100A8, and S100A9. Finally, the innate immune molecular mechanisms of adjuvant action of AJSAF and the potential signatures were proposed. These findings expanded the current knowledge on the mechanisms of action of saponin-based adjuvants.