Zerbib Yoann, Jenkins Emily K, Shojaei Maryam, Meyers Adrienne F A, Ho John, Ball T Blake, Keynan Yoav, Pisipati Amarnath, Kumar Aseem, Kumar Anand, Nalos Marek, Tang Benjamin M, Schughart Klaus, McLean Anthony
Department of medical Intensive Care, Amiens University Hospital, Amiens, France.
Department of Intensive Care Medicine, Nepean Hospital, Sydney, Australia.
BMC Med Genomics. 2020 Feb 17;13(1):28. doi: 10.1186/s12920-020-0672-7.
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.
流感感染会导致一系列疾病严重程度，从轻度呼吸道疾病到呼吸衰竭甚至死亡。与进展为重症流感疾病相关的宿主反应途径尚未完全了解。
为深入了解与进展为严重感染相关的疾病机制，我们分析了重症和中度流感患者以及健康对照者的白细胞转录组。使用基于拓扑结构的途径分析工具对差异表达基因进行途径分析，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，以阐明从中度流感进展为重度流感的生物学机制。
该研究纳入了107名患者（44名重症流感患者和63名中度流感患者）和52名健康对照者。重症流感与几种中性粒细胞相关途径的上调有关，包括参与中性粒细胞分化、迁移、脱颗粒和中性粒细胞胞外陷阱（NET）形成的途径。与中度感染患者相比，重症感染患者中性粒细胞相关途径的上调程度明显更高。重症流感还与免疫反应途径的下调有关，包括参与抗原呈递的途径，如CD4+T细胞共刺激、CD8+T细胞和自然杀伤（NK）细胞效应功能。与中度和健康对照相比，重症流感患者的凋亡途径也下调。
这些发现表明基因表达谱存在变化，这可能突出了与从中度流感进展为重度流感感染相关的不同致病机制。
