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Histological Quantification to Determine Lung Fungal Burden in Experimental Aspergillosis
Published on: March 9, 2018
Longitudinal In Vivo Assessment of Host-Microbe Interactions in a Murine Model of Pulmonary Aspergillosis
Shweta Saini1, Jennifer Poelmans1, Hannelie Korf2
1Biomedical MRI/Molecular Small Animal Imaging Center (MoSAIC), KU Leuven, Leuven, Belgium.
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.
Insights
This study introduces fluorine-19 magnetic resonance imaging (19F MRI) as a novel tool to non-invasively monitor immune responses against invasive pulmonary aspergillosis (IPA). It enables tracking of immune cells in vivo, offering new insights into host-pathogen interactions.
Area of Science:
- Immunology
- Medical Imaging
- Mycology
Background:
- Invasive pulmonary aspergillosis (IPA) is a serious fungal infection caused by Aspergillus fumigatus, particularly in immunocompromised individuals.
- Understanding the host immune response is crucial for controlling IPA, but non-invasive assessment tools have been lacking.
- Host-microbe interactions in IPA pathogenesis remain incompletely understood due to limited monitoring capabilities.
Purpose of the Study:
- To develop and validate a non-invasive imaging method for longitudinal assessment of the host immune response against IPA in vivo.
- To utilize fluorine-19 magnetic resonance imaging (19F MRI) for tracking immune cells involved in the host defense against Aspergillus fumigatus.
- To investigate the impact of immunosuppression on the immune microenvironment during IPA.
Main Methods:
- Development of a novel 19F MRI methodology for in vivo imaging.
- Utilized a perfluorocarbon-based contrast agent for in vivo labeling of immune cells, specifically macrophages and dendritic cells.
- Applied the technique to murine models of invasive pulmonary aspergillosis to quantify pulmonary inflammation longitudinally.
Main Results:
- Demonstrated the efficacy of 19F MRI with a perfluorocarbon agent for in vivo immune cell labeling in IPA models.
- Successfully quantified pulmonary inflammation and assessed the kinetics of the innate immune response.
- Identified a permissive niche created by immunosuppression that facilitates fungal growth.
Conclusions:
- 19F MRI is a powerful, non-invasive tool for longitudinally studying host immune responses in invasive pulmonary aspergillosis.
- The technique allows for real-time assessment of innate immune cell dynamics and the impact of immunosuppression.
- This advancement holds significant potential for improving the understanding and management of IPA in vulnerable patient populations.
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