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: since 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 442860406

The environmental mould Aspergillus fumigatus is a prevalent cause of allergic lung inflammation that can manifest as allergic bronchopulmonary aspergillosis, ABPA. Eosinophilic granulocytes play a pivotal role in the immune response to allergic inflammation but the interaction of these effector cells with the fungal pathogen in the corresponding context is not well understood. Prior efforts of the collaborating research teams have scrutinized the antifungal activity of eosinophils against A. fumigatus and their activation when encountering this fungal pathogen. Crucial components of the relevant signalling cascades that are involved in eosinophil activation by A. fumigatus could be validated. With respect to fungal traits that are relevant in this context, an influence of extracellular proteolytic activities could be demonstrated; moreover, fungal transcription factors that shape the transcriptome upon interaction with eosinophils were identified and await further characterisation. Based on these prior results, specific research aims shall be addressed in the next funding period, such as the role of A. fumigatus extracellular proteases and the PAR-2 receptor in the context of human eosinophil activation as well as the cellular function of fungal transcription factors affecting this interaction. Moreover, the impact of A. fumigatus-activated eosinophils on gene expression and metabolism of other cells in the pulmonary environment shall be scrutinized and the effect of this interplay on lung epithelial cells will be addressed in sophisticated cell culture models, such as lung organoids. All these complementary efforts hold the promise to shed light on an understudied scenario at the fungal pathogen / host immunity interface.

• DFG Programme: Research Grants