Cross-talk of Aspergillus fumigatus with neutrophilic granulocytes

Neutrophils are the most important effector cells in the immune response against Aspergillus fumigatus. In project A1, we aim at understanding the mechanisms how neutrophils control A. fumigatus infections.

In the first funding period we developed novel methods for the bioinformatics-based analysis of live cell imaging. This allowed automated quantification of phagocytosis and the identification of fungal molecules inhibiting phagocytosis. Furthermore, quantitative analysis of the dual proteome of A. fumigatus and neutrophils by LC-MS was established. This led to the discovery of novel human proteins involved in the interactions with this fungus.

In the second funding period our research will focus on the identification of novel effector mechanisms of neutrophils against A. fumigatus, building on our discoveries from the first funding period. We will also characterize immune cell receptors potentially involved in the cross-talk of neutrophils with A. fumigatus. For this, we will use immune cells from knockout mice, cell lines, monoclonal antibodies that block specific receptors and mouse infection models for invasive aspergillosis. Finally, we will analyze patient groups for single nucleotide polymorphisms (SNPs) in the proteins that interact with A. fumigatus as basis for translational approaches.