Abstract
ABSTRACT 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.
Highlights
With over 200,000 annual cases world-wide, Aspergillus fumigatus is the most common cause of fungal lung infections in immunocompromised patients [1,2]
We identified several allergens, AspF2 (M6), Crf1 (M7), and AspF4 (M8), which were predominantly detected in infected mice and have pre viously been identified in Allergic bronchopulmonary aspergillosis (ABPA) patients as strong immunogenic fungal antigens (Table 3) [34,35,36,37]
We performed a comprehensive analysis of host protein changes during Invasive pulmonary aspergillosis (IPA) in human and mice and compared protein profiles in both hosts to allow a definition of particular host biomarkers that are spe cifically enriched in samples positive for IPA
Summary
With over 200,000 annual cases world-wide, Aspergillus fumigatus is the most common cause of fungal lung infections in immunocompromised patients [1,2]. In recent years several publica tions have aimed to determine secreted fungal anti gens associated with Aspergillus invasion that could serve as potential biomarkers for faster and more sensitive and specific diagnosis of IPA [3,4,5,6,7,8]. Most of these studies used immunoblotting of fungal pro tein extracts derived from fungal in vitro cultures with patient sera containing anti- Aspergillus antibo dies to detect infection-specific antigens [4,7]. It allows monitoring of pulmonary fungal growth by in vivo imaging [12,13]
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