School of Public Health (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen, China.
School of Public Health (Shenzhen), Sun Yat-sen University, Guangzhou, China.
Front Immunol. 2023 Jan 12;13:1048774. doi: 10.3389/fimmu.2022.1048774. eCollection 2022.
Influenza susceptibility difference is a widely existing trait that has great practical significance for the accurate prevention and control of influenza.
Here, we focused on the human susceptibility to the seasonal influenza A/H3N2 of healthy adults at baseline level. Whole blood expression data for influenza A/H3N2 susceptibility from GEO were collected firstly (30 symptomatic and 19 asymptomatic). Then to explore the differences at baseline, a suite of systems biology approaches - the differential expression analysis, co-expression network analysis, and immune cell frequencies analysis were utilized.
We found the baseline condition, especially immune condition between symptomatic and asymptomatic, was different. Co-expression module that is positively related to asymptomatic is also related to immune cell type of naïve B cell. Function enrichment analysis showed significantly correlation with "B cell receptor signaling pathway", "immune response-activating cell surface receptor signaling pathway" and so on. Also, modules that are positively related to symptomatic are also correlated to immune cell type of neutrophils, with function enrichment analysis showing significantly correlations with "response to bacterium", "inflammatory response", "cAMP-dependent protein kinase complex" and so on. Responses of symptomatic and asymptomatic hosts after virus exposure show differences on resisting the virus, with more effective frontline defense for asymptomatic hosts. A prediction model was also built based on only baseline transcription information to differentiate symptomatic and asymptomatic population with accuracy of 0.79.
The results not only improve our understanding of the immune system and influenza susceptibility, but also provide a new direction for precise and targeted prevention and therapy of influenza.
流感易感性差异是一个广泛存在的特征，对流感的准确预防和控制具有重要的实际意义。
在这里，我们主要关注健康成年人在基线水平上对季节性甲型流感 A/H3N2 的易感性。首先从 GEO 中收集了甲型流感 A/H3N2 易感性的全血表达数据（30 例有症状和 19 例无症状）。然后，为了探索基线水平的差异，我们采用了一系列系统生物学方法——差异表达分析、共表达网络分析和免疫细胞频率分析。
我们发现，无症状和有症状患者的基线状态，特别是免疫状态存在差异。与无症状呈正相关的共表达模块也与未成熟 B 细胞的免疫细胞类型有关。功能富集分析显示与“B 细胞受体信号通路”、“免疫反应激活细胞表面受体信号通路”等显著相关。同样，与有症状呈正相关的模块也与中性粒细胞的免疫细胞类型相关，功能富集分析显示与“对细菌的反应”、“炎症反应”、“cAMP 依赖性蛋白激酶复合物”等显著相关。病毒感染后，有症状和无症状宿主的反应存在差异，无症状宿主的前线防御更为有效。还基于仅基线转录信息建立了一个预测模型，以区分有症状和无症状人群，准确率为 0.79。
这些结果不仅提高了我们对免疫系统和流感易感性的认识，而且为流感的精确和靶向预防和治疗提供了新的方向。
