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

Fungal infections in a context of pre-existing immunodeficiency or lung disease are often life-threatening complications, but our knowledge on 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 in this paradoxical role of immune cells. To address these challenges, preclinical investigators typically rely on end-stage analyses on 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 a novel strategy to treat azole-resistant aspergillosis. We will innovate dual-channel imaging in order to follow up the pathogen ànd its interaction with host cells in vivo that will enable us to unravel the hypothesized dual role of macrophages in providing defense as well as a vehicle for fungal dissemination. We will thereby deliver a generic lung imaging platform to the Pneumology field, amendable to other lung diseases requiring insights into the host-pathogen relationship in a dynamic, translational manner.