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

Fungal infections in the context of pre-existing immunodeficiency or lung disease are often life-threatening complications, but our knowledge of the interplay of pathogen and host factors involved still contains important therapeutic, methodological and fundamental gaps. Resistance against current antifungal therapy urges us to find alternatives. Host factors inhibit or facilitate infection dissemination, and we lack insight into this paradoxical role of immune cells. To address these challenges, preclinical investigators typically rely on end-stage analyses of experimental models that are useful, but inherently limited to a snapshot of pathogen- or host-related processes that are essentially dynamic in time and space. As repeated follow-up is indispensable to untangle these dynamic processes, we here aim to close the gaps by delivering novel longitudinal imaging-derived biomarkers on lung disease burden, infection status and host response, here applied to fungal infections. We will innovate dual-channel imaging in order to follow up on the pathogen and its interaction with host cells in vivo which will enable us to unravel the hypothesized dual role of macrophages in providing defence as well as a vehicle for fungal dissemination. We will thereby deliver a generic lung imaging platform, amendable to other lung diseases requiring insights into the host-pathogen relationship in a dynamic, translational manner.