Abstract
Opportunistic human pathogenic fungi including the saprotrophic mold Aspergillus fumigatus and the human commensal Candida albicans can cause severe fungal infections in immunocompromised or critically ill patients. The first line of defense against opportunistic fungal pathogens is the innate immune system. Phagocytes such as macrophages, neutrophils and dendritic cells are an important pillar of the innate immune response and have evolved versatile defense strategies against microbial pathogens. On the other hand, human-pathogenic fungi have sophisticated virulence strategies to counteract the innate immune defense. In this context, proteomic approaches can provide deeper insights into the molecular mechanisms of the interaction of host immune cells with fungal pathogens. This is crucial for the identification of both diagnostic biomarkers for fungal infections and therapeutic targets. Studying host-fungal interactions at the protein level is a challenging endeavor, yet there are few studies that have been undertaken. This review draws attention to proteomic techniques and their application to fungal pathogens and to challenges, difficulties, and limitations that may arise in the course of simultaneous dual proteome analysis of host immune cells interacting with diverse morphotypes of fungal pathogens. On this basis, we discuss strategies to overcome these multifaceted experimental and analytical challenges including the viability of immune cells during co-cultivation, the increased and heterogeneous protein complexity of the host proteome dynamically interacting with the fungal proteome, and the demands on normalization strategies in terms of relative quantitative proteome analysis.
Highlights
Superficial, non-life-threatening infections of the human skin, nails and mucosa are the most common fungal diseases in humans and affect around one quarter of the world population., Infectious diseases caused by fungi contribute substantially to human morbidity and mortality
Immunocompromised patients are vulnerable to these fungal killers, whereas invasive fungal infections are extremely rare in immunocompetent individuals [2]
Further evidence is that invasive mold infections occur mainly in neutropenic individuals and chronic granulomatous disease (CGD) patients, whose neutrophils lack the capability of producing oxidative burst [115]
Summary
Superficial, non-life-threatening infections of the human skin, nails and mucosa are the most common fungal diseases in humans and affect around one quarter of the world population., Infectious diseases caused by fungi contribute substantially to human morbidity and mortality. It causes little or no disease in healthy individuals. In addition to the aforementioned fungi, several other species are able to cause severe diseases in humans Their occurrence is either restricted to a specific region of the world or the frequency of infections is relatively rare.mucormycosis has emerged as the third most common invasive infection after candidiasis and aspergillosis in patients with hematological malignancies and allogeneic stem cell transplantation. Macrophages are the first cells to encounter an invading fungus They recognize fungal pathogens via pathogen-associated molecular patterns (PAMPs), phagocytose, and consecutively kill them intracellularly. We review current efforts and strategies to investigate the proteomic changes during interaction of pathogenic fungi with immune effector cells in the human host. We give a brief overview about the investigation of fungal-specific serum antibody signatures in patients with invasive mycoses
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