This application focuses on the characterization of the interaction between Aspergillus fumigatus and human dendritic cells and macrophages and the subsequent induction of innate and pathogen-specific adaptive immune responses. The potential role of Toll-like receptors (TLRs) for Aspergillus fumigatusmediated activation of different DC subsets, macrophages and granulocytes will be studied systematically in established cell culture models using wild-type and TLR-deficient human and murine cells, and luciferase reporter assays. In addition, the role of frequent TLR2 and 4 polymorphisms for Aspergillus fumigatus-induced cell activation will be analyzed. Moreover, TH-cell responses induced by Aspergillus fumigatus-activated DCs will be characterized focusing on the identification of target proteins, HLA-restriction, dominant TCR-usage and cytokines secreted upon stimulation. These investigations will be supplemented by a prospective analysis of the Aspergillus fumigatus-directed innate and adaptive immune responses in recipients of an allogeneic stem cell transplantat to define the clinical impact of these immune effector mechanisms in the control of invasive aspergillosis.
DFG Programme
Priority Programmes
