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Project

Multimodal dual-imaging-derived biomarkers for unravelling host response from lung disease progression in cystic lung fibrosis, infection and therapy

Despite the significant advances made by the introduction of imaging techniques for lung diseases and fungal infection research, there are still important gaps where we identify three priorities we want to address with our project. First, we will address the need for alternative antifungal treatment approaches by investigating fungicidal combinatorial treatment in vivo in mouse models of invasive pulmonary aspergillosis (IPA) (context of immune deficiency) and allergic aspergillosis (in the context of cystic fibrosis) after infection with azolesusceptible and -resistant A. fumigatus using multimodal imaging. With our multimodal imaging approach, we are currently able to follow one dynamic in vivo process or one cell population at a time per imaging modality, such as fungal load ('1-channel, multimodal'). Monitoring two cell populations simultaneously is currently unavailable, which is nevertheless relevant to understand the pathogenesis of lung disease in interaction with the immune system, or evaluate the interactions of two pathogen populations, such as in realistic mixed infection settings. Therefore the second objective of this project is to simultaneously track two processes, such as host (immune) response in parallel with pathogen proliferation during fungal infection progression/dissemination (“2-channel, multimodal”). Thirdly, the paradoxical role of the host’s immune cells in e.g. exacerbation or the crucial event of infection dissemination to the brain such as in cryptococcosis, remains unclear. To address this, we will implement our newly developed dual-channel multimodal imaging methods in our established mouse models of pulmonary and cerebral cryptococcosis, to image cryptococcal cells and macrophages simultaneously to analyze the interaction of the pathogen and host macrophages. This will increase our understanding of the immune systems’ paradoxical role and the host-pathogen interactions underlying both protection against and dissemination of infection, and ultimately lead to the identification of novel therapeutic targets in the management of (exacerbation of) lung diseases by fungal infections.

Date:15 Oct 2020 →  Today
Keywords:multimodal dual imaging, fungal infection, cryptococcosis, immune response, lung-to-brain dissemination, preclinical models, lung disease
Disciplines:Respiratory medicine, Medical imaging and therapy not elsewhere classified, Infectious diseases, Adaptive immunology, Innate immunity
Project type:PhD project