Analysis of the interaction between Aspergillus fumigatus and human immune effector cells and the induction of innate and adaptive immune responses to the pathogen

• Applicant: Professor Dr. Hermann Einsele
• Subject Area: Parasitology and Biology of Tropical Infectious Disease Pathogens
• Term: from 2004 to 2010
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5427064

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
• Subproject of: SPP 1160: Colonisation and Infection by Human-pathogenic Fungi
• Participating Person: Professor Dr. Jürgen Löffler