Influenza infections produce a spectrum of disease severity, ranging from a mild respiratory illness to respiratory failure and death. The host-response pathways associated with the progression to severe influenza disease are not well understood. To gain insight into the disease mechanisms associated with progression to severe infection, we analyzed the leukocyte transcriptome in severe and moderate influenza patients and healthy control subjects. Pathway analysis on differentially expressed genes was performed using a topology-based pathway analysis tool that takes into account the interaction between multiple cellular pathways. The pathway profiles between moderate and severe influenza were then compared to delineate the biological mechanisms underpinning the progression from moderate to severe influenza. 107 patients (44 severe and 63 moderate influenza patients) and 52 healthy control subjects were included in the study. Severe influenza was associated with upregulation in several neutrophil-related pathways, including pathways involved in neutrophil differentiation, migration, degranulation and neutrophil extracellular trap (NET) formation. The degree of upregulation in neutrophil-related pathways were significantly higher in severely infected patients compared to moderately infected patients. Severe influenza was also associated with downregulation in immune response pathways, including pathways involved in antigen presentation such as CD4+ T-cell co-stimulation, CD8+ T cell and Natural Killer (NK) cells effector functions. Apoptosis pathways were also downregulated in severe influenza patients compare to moderate and healthy controls. These findings showed that there are changes in gene expression profile that may highlight distinct pathogenic mechanisms associated with progression from moderate to severe influenza infection.

中文翻译：

---

流感患者中白细胞转录组的途径定位揭示了与严重感染进展相关的独特致病机制

流感感染会引起一系列疾病严重程度，从轻度呼吸道疾病到呼吸衰竭和死亡。与进展为严重的流感疾病有关的宿主反应途径还不是很清楚。为了深入了解与严重感染进展相关的疾病机制，我们分析了重度和中度流感患者以及健康对照组的白细胞转录组。使用基于拓扑的途径分析工具对差异表达基因进行了途径分析，该工具考虑了多个细胞途径之间的相互作用。然后比较中度和重度流感之间的途径概况，以描述支持从中度到重度流感发展的生物学机制。研究包括107例患者（44例重症和63例中度流感患者）和52例健康对照者。严重的流感与中性粒细胞相关的几种途径的上调相关，包括与中性粒细胞分化，迁移，脱粒和中性粒细胞胞外捕获（NET）形成有关的途径。与中度感染患者相比，重度感染患者中性粒细胞相关途径的上调程度明显更高。严重的流感还与免疫反应途径的下调相关，包括抗原呈递所涉及的途径，例如CD4 + T细胞共刺激，CD8 + T细胞和自然杀伤（NK）细胞效应子功能。与中度和健康对照组相比，重症流感患者的细胞凋亡途径也被下调。