Unravelling the pathogenic mechanism behind influenza-associated pulmonary aspergillosis.
Invasive pulmonary aspergillosis (IPA) is a life-threatening infection occurring mainly in immunocompromised patients. However, recently severe influenza infection gains a foothold worldwide as a novel emerging risk factor for IPA in critically ill patients. Despite notable advances in clinical observations, the mechanism underlying influenza-associated pulmonary aspergillosis (IAPA) remains unknown. Therefore, this project aims to provide fundamental knowledge in the pathogenic mechanism and the contribution of different pathophysiological factors leading to IAPA by using state-of-the-art immunophenotyping by flow cytometry, complementary key cytokine analysis, treatment studies, and small-animal imaging tools (µCT and BLI). Hence, I will first elucidate the dose-response between the severity of influenza and the susceptibility to IPA by modulating influenza with oseltamivir and baloxavir marboxil treatment in an influenza-Aspergillus mouse model. Secondly, I will unravel the pathogenic mechanism behind IAPA via in-depth state-of-the-art immunological research. Finally, I will identify the specificity of influenza towards the development of IPA by comparing it to one other viral infection (e.g. respiratory syncytial virus). Ultimately, this project will lead to novel and innovative insights regarding pathophysiology and influence of antiviral treatments on IAPA disease. Translating this knowledge could lead to new starting points for future management of IAPA.