Department of Intensive Care Medicine, Nepean Hospital, Sydney, Australia.
Centre for Immunology and Allergy Research, The Westmead Institute for Medical Research, Sydney, Australia.
Nat Commun. 2019 Jul 31;10(1):3422. doi: 10.1038/s41467-019-11249-y.
Severe influenza infection has no effective treatment available. One of the key barriers to developing host-directed therapy is a lack of reliable prognostic factors needed to guide such therapy. Here, we use a network analysis approach to identify host factors associated with severe influenza and fatal outcome. In influenza patients with moderate-to-severe diseases, we uncover a complex landscape of immunological pathways, with the main changes occurring in pathways related to circulating neutrophils. Patients with severe disease display excessive neutrophil extracellular traps formation, neutrophil-inflammation and delayed apoptosis, all of which have been associated with fatal outcome in animal models. Excessive neutrophil activation correlates with worsening oxygenation impairment and predicted fatal outcome (AUROC 0.817-0.898). These findings provide new evidence that neutrophil-dominated host response is associated with poor outcomes. Measuring neutrophil-related changes may improve risk stratification and patient selection, a critical first step in developing host-directed immune therapy.
严重流感感染目前尚无有效的治疗方法。开发针对宿主的治疗方法的主要障碍之一是缺乏可靠的预后因素来指导这种治疗。在这里，我们使用网络分析方法来确定与严重流感和致命结局相关的宿主因素。在患有中重度疾病的流感患者中，我们发现了一个复杂的免疫途径景观，主要变化发生在与循环中性粒细胞相关的途径中。严重疾病患者表现出过度的中性粒细胞细胞外陷阱形成、中性粒细胞炎症和延迟凋亡，所有这些都与动物模型中的致命结局相关。过度的中性粒细胞激活与恶化的氧合损伤和预测的致命结局相关（AUROC 0.817-0.898）。这些发现提供了新的证据，表明以中性粒细胞为主的宿主反应与不良结局相关。测量与中性粒细胞相关的变化可能会改善风险分层和患者选择，这是开发针对宿主的免疫治疗的关键第一步。
