Crosstalk between eosinophils and Aspergillus fumigatus during allergic lung inflammation

• Applicants: Professor Dr. Sven Krappmann; Professor Dr. David Vöhringer
• Subject Area: Medical Microbiology and Mycology, Hygiene, Molecular Infection Biology ; Immunology
• Term: from 2020 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 442860406

Allergic bronchopulmonary aspergillosis (ABPA) is a complex hypersensitivity pneumonitis that is caused predominantly by the omnipresent environmental mould Aspergillus fumigatus to affect patients suffering from asthma or cystic fibrosis. Eosinophilic granulocytes and their secreted cytokines play a pivotal role for the immunopathology of this inflammatory allergic response towards fungal elements. However in this context, major knowledge gaps exist with respect to the exact immunological mechanisms and effects that drive ABPA. Preliminary activities of both research groups have revealed that murine eosinophils become activated to act fungicidal in a contact-dependent manner when encountering A. fumigatus cells, and have established a murine infection model of ABPA to demonstrate massive lung eosinophilia after repeated administration of live A. fumigatus conidia. Joint efforts have recently resulted in a publication clarifying the role of a signaling adaptor for eosinophil development and allergic lung eosinophilia in mice. To now address the host response as well as fungal determinants in a more comprehensive and complementary manner, this research proposal aims at clarifying three major aspects of ABPA: A. fumigatus-derived factors that act on murine and human eosinophils together with the corresponding receptors and signaling pathways shall be identified, the transcriptional response and regulation thereof in eosinophils and fungal cells upon confrontation will be monitored, and the dynamic interaction between both cellular partners in the course of ABPA will be assessed in vivo by making use of an established murine infection model. Complementary experimental tasks are scheduled according to the applicants’ scientific expertise of strong immunological and fungal molecular biology background, respectively. Based on this unique combination of scientific expertise, the proposed efforts will shed light on relevant aspects of this complex allergic disease to provide therapeutic perspectives for patients suffering from ABPA.

• DFG Programme: Research Grants