Longitudinal In Vivo Assessment of Host-Microbe Interactions in a Murine Model of Pulmonary Aspergillosis.

Abstract

The fungus Aspergillus fumigatus is ubiquitous in nature and the most common cause of invasive pulmonary aspergillosis (IPA) in patients with a compromised immune system. The development of IPA in patients under immunosuppressive treatment or in patients with primary immunodeficiency demonstrates the importance of the host immune response in controlling aspergillosis. However, study of the host-microbe interaction has been hampered by the lack of tools for their non-invasive assessment. We developed a methodology to study the response of the host's immune system against IPA longitudinally in vivo by using fluorine-19 magnetic resonance imaging (19F MRI). We showed the advantage of a perfluorocarbon-based contrast agent for the in vivo labeling of macrophages and dendritic cells, permitting quantification of pulmonary inflammation in different murine IPA models. Our findings reveal the potential of 19F MRI for the assessment of rapid kinetics of innate immune response against IPA and the permissive niche generated through immunosuppression.We are grateful for the financial support by the following funding agencies: the European Commission Marie Curie (ITN) BetaTrain (289932), the Research Foundation Flanders (FWO, G.0A75.14, G.0B28.14, and G.069115N), the Agentschap voor Innovatie door Wetenschap en Technologie for the SBO NanoCoMIT (IWT SBO 140061), the European ERA-NET project “CryptoView” (third call of the FP7 programme Infect-ERA), and KU Leuven for PF 10/017 (IMIR)

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