Third party funded individual grant
Acronym: VO944/11-1
Start date : 01.07.2020
End date : 31.03.2024
Allergic lung inflammation caused by the omnipresent environmental mould Aspergillus fumigatus can result in bronchopulmonary aspergillosis (ABPA) which affects 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 A. fumigatus-elicited allergic lung inflammation. 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 to demonstrate massive lung eosinophilia after repeated administration of live A. fumigatus conidia. Joint efforts have 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: 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 A. fumigatus-elicited allergic lung inflammation 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 immune response to provide therapeutic perspectives for patients suffering from A. fumigatus-induced allergic lung inflammation including ABPA.