IFN-dependent macrophage-intrinsic innate resistance to Legionella pneumophila

• Applicant: Professor Dr. Bastian Opitz
• Subject Area: Parasitology and Biology of Tropical Infectious Disease Pathogens
• Term: from 2014 to 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 261089381

While intracellular pathogens, such as L. pneumophila, manipulate host cell processes in order to establish an intracellular niche for their survival and replication, host cells have evolved defense pathways to restrict the infection. We will examine an intracellular innate resistance mechanism activated by type I and II IFNs that restricts L. pneumophila infection. Based on preliminary data, we hypothesize that both types of IFNs stimulate the localization of antibacterial proteins to the Legionella containing vacuole (LCV). Candidate proteins will be identified by quantitative proteomic analyses of LCVs of IFNbeta and IFNgamma treated or untreated macrophages. The function of these proteins will be investigated by siRNA mediated gene silencing, overexpression and confocal microscopy. Studies of human cells will verify whether a potentially existing weakness of the IFN mediated resistance contributes to the susceptibility of human cells (and patients) towards L. pneumophila infection. Collectively, this project will provide insights in the defence mechanisms against intracellular bacteria and will identify antimicrobial proteins that might represent novel targets for therapeutic interventions.

• DFG Programme: Priority Programmes
• Subproject of: SPP 1580: Intracellular Compartments as Places of Pathogen-Host Interaction