INSERM, U945, 75013 Paris, France.
J Proteomics. 2012 May 17;75(9):2536-49. doi: 10.1016/j.jprot.2012.01.040. Epub 2012 Feb 17.
Invasive aspergillosis (IA) is a major threat for immunocompromised patients. Diagnostic difficulties often delay specific treatment initiation, which increases mortality. Finding new biomarkers to improve and speed accurate diagnosis is thus vital. To investigate the ability of proteomic methods for discovering new biomarkers of IA, we used a DIGE approach to perform a proteomic analysis on both bronchoalveolar lavages (BAL) and sera at different time-points of infection in a mouse model of invasive pulmonary aspergillosis. Progression of the infection was monitored using a bioluminescent strain of Aspergillus fumigatus. Sera proteins were enriched using the ProteoMiner kit (Biorad). This method allowed us to identify a fungal protein, the A. fumigatus major allergen Asp f 2, in sera of mice one day after the infection. However, this fungal protein was not detected three days after the infection. Importantly, in BAL, this work provides evidence of an in vivo complement evasion mechanism through the cleavage of C3b into three fragments during aspergillosis. Finally, our results underlining the inflammatory host response to IA in both lung and blood compartments at different times of infection may provide new insights into the pathophysiology of this disease.
侵袭性曲霉病(IA)是免疫功能低下患者的主要威胁。诊断困难常常导致特异性治疗的延迟,从而增加死亡率。因此,寻找新的生物标志物来改善和加速准确诊断至关重要。为了研究蛋白质组学方法在发现 IA 新生物标志物方面的能力,我们使用 DIGE 方法对侵袭性肺曲霉病小鼠模型的支气管肺泡灌洗液(BAL)和血清在感染不同时间点进行了蛋白质组学分析。使用烟曲霉的生物发光株监测感染的进展。使用 ProteoMiner 试剂盒(Biorad)对血清蛋白进行富集。该方法使我们能够在感染后一天的小鼠血清中鉴定出一种真菌蛋白,烟曲霉主要过敏原 Asp f 2。然而,在感染后三天并未检测到这种真菌蛋白。重要的是,在 BAL 中,这项工作提供了在体内通过补体 C3b 在曲霉病过程中切割成三个片段来逃避补体的证据。最后,我们的结果强调了宿主对 IA 的炎症反应,在感染的不同时间点在肺部和血液两个部位都有反应,这可能为该疾病的病理生理学提供新的见解。