Department of Pediatrics, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania, United States of America.
PLoS One. 2013 Dec 6;8(12):e82865. doi: 10.1371/journal.pone.0082865. eCollection 2013.
Influenza viruses pose a significant health risk and annually impose a great cost to patients and the health care system. The molecular determinants of influenza severity, often exacerbated by secondary bacterial infection, are largely unclear. We generated a novel outbred mouse model of influenza virus, Staphylococcus aureus, and co-infection utilizing influenza A/CA/07/2009 virus and S. aureus (USA300). Outbred mice displayed a wide range of pathologic phenotypes following influenza virus or co-infection ranging broadly in severity. Influenza viral burden positively correlated with weight loss although lung histopathology did not. Inflammatory cytokines including IL-6, TNF-α, G-CSF, and CXCL10 positively correlated with both weight loss and viral burden. In S. aureus infection, IL-1β, G-CSF, TNF-α, and IL-6 positively correlated with weight loss and bacterial burden. In co-infection, IL-1β production correlated with decreased weight loss suggesting a protective role. The data demonstrate an approach to identify biomarkers of severe disease and to understand pathogenic mechanisms in pneumonia.
流感病毒对健康构成重大威胁，每年给患者和医疗保健系统带来巨大负担。流感严重程度的分子决定因素，往往因继发细菌感染而加重，在很大程度上尚不清楚。我们利用甲型流感病毒 A/CA/07/2009 株和金黄色葡萄球菌（USA300），创建了一种新型的流感病毒、金黄色葡萄球菌和合并感染的远交系小鼠模型。远交系小鼠在感染流感病毒或合并感染后表现出广泛的病理表型，严重程度差异很大。流感病毒载量与体重减轻呈正相关，尽管肺组织病理学检查结果并非如此。包括 IL-6、TNF-α、G-CSF 和 CXCL10 在内的炎症细胞因子与体重减轻和病毒载量均呈正相关。在金黄色葡萄球菌感染中，IL-1β、G-CSF、TNF-α 和 IL-6 与体重减轻和细菌载量呈正相关。在合并感染中，IL-1β 的产生与体重减轻减少相关，提示其具有保护作用。这些数据表明了一种识别严重疾病生物标志物和了解肺炎发病机制的方法。
