Proteome analysis of bronchoalveolar lavage fluids reveals host and fungal proteins highly expressed during invasive pulmonary aspergillosis in mice and humans

Invasive pulmonary aspergillosis (IPA) is a severe infection that is difficult to diagnose due to the ubiquitous presence of fungal spores, the underlying diseases of risk patients, and limitations of currently available markers. In this study, we performed a comprehensive liquid chromatography tandem mass spectrometry (LC-MS/MS)-based identification of host and fungal proteins expressed during IPA in mice and humans. The proteomic analysis of bronchoalveolar lavage samples of individual IPA and control cases allowed the description of common host factors that had significantly increased abundance in both infected animals and IPA patients compared to their controls. Although increased levels of these individual host proteins might not be sufficient to distinguish bacterial from fungal infection, a combination of these markers might be beneficial to improve diagnosis. We also identified 16 fungal proteins that were specifically detected during infection and may be valuable candidates for biomarker evaluation.

侵袭性肺曲霉病（Invasive pulmonary aspergillosis, IPA）是一种重症感染，由于真菌孢子广泛存在、高危患者伴有基础疾病，且当前可用的检测标志物存在局限性，其诊断难度极高。本研究基于液相色谱串联质谱（liquid chromatography tandem mass spectrometry, LC-MS/MS）技术，对小鼠与人类罹患侵袭性肺曲霉病过程中表达的宿主及真菌蛋白开展了全面鉴定。通过对侵袭性肺曲霉病病例与对照病例的支气管肺泡灌洗液样本进行蛋白质组学分析，我们明确了一类共同的宿主因子：相较于各自对应的对照组，该类因子在感染动物及IPA患者体内的丰度均显著升高。尽管此类单个宿主蛋白的水平升高或许不足以区分细菌感染与真菌感染，但将这些标志物联合应用，或可有效提升诊断效能。本研究同时鉴定出16种仅在感染过程中可被检测到的真菌蛋白，它们或可作为生物标志物（biomarker）研发的潜在候选对象。