Infection and iron metabolism are inevitably interconnected. This principle can be also applied to infection with the ubiquitous saprophytic fungus Aspergillus fumigatus, which is the most prevalent airborne fungal pathogen causing live-threatening invasive aspergillosis in immuno-comprised patients. Due to limited diagnostical as well as therapy options, this fungal disease is still associated with a high mortality rate. Treatment and management of opportunistic infections are becoming increasingly important, as more and more immunosuppressive regiments in medical interventions are being established. Not only in transplantation but also in patients undergoing cancer chemotherapy, immunosupression is becoming a relevant topic. A. fumigatus releases airborne conidia abundantly, which are inevitably and constantly inhaled with the breathing air. In immune-competent hosts, alveolar macrophages are critical for the first line of defense by detecting and phagocytosing conidia. Intensive research in the past years revealed that fungal-specific ferric iron chelators, termed siderophores, are expressed by this pathogen. These chelators are involved in iron uptake as well as iron storage.
With the help of iron specific knock-out models on the one hand and iron metabolism-defective A. fumigatus mutant strains on the other hand the aim of this project is to analyze the link between iron-dependent host immune response and fungal iron homeostasis. The knowledge on underlying molecular mechanisms and relevant interactions are expected to improve treatment options for this opportunistic disease.
