Sensitive bioluminescence imaging of fungal dissemination to the brain in mouse models of cryptococcosis
| Autor: | Matthias Brock, Liesbeth Vanherp, Amy Hillen, Guilhem Janbon, Katrien Lagrou, Alexandra Ristani, Jennifer Poelmans, Uwe Himmelreich, Greetje Vande Velde |
|---|---|
| Přispěvatelé: | Biomedical MRI [Leuven], Department of Imaging and Pathology [Leuven], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven)-Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), core facility Molecular Small Animal Imaging Center (Leuven) (MoSAIC), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Université Catholique de Louvain = Catholic University of Louvain (UCL), Laboratory of Clinical Bacteriology and Mycology [Leuven], Department of Microbiology, Immunology and Transplantation [Leuven], Biologie des ARN des Pathogènes fongiques - RNA Biology of Fungal Pathogens, Institut Pasteur [Paris], School of Life Sciences, University of Nottingham, UK (UON), This work was funded by the European Commission ERA-NET project ‘CryptoView’ (third call of the FP7 program Infect-ERA), the Research Foundation-Flanders (FWO, Fonds Wetenschappelijk Onderzoek, 1506114N) and KU Leuven [PF 10/017 (IMIR), CREA/14/015]. L.V. is a PhD fellow strategic basic research at the FWO (151313). J.P. received a PhD grant for strategic basic research from the Agency for Innovation by Science and Technology (IWT, 141230). G.V.V. received a postdoctoral fellowship from the FWO (12N7615N)., The authors thank Kristof Govaerts for his assistance with the MRI quantification, Dr Lore Pollaris for guidance with the endotracheal model and all partners involved in the ERA-NET project ‘CryptoView’ for the fruitful discussions., European Project: 321529,EC:FP7:HEALTH,FP7-ERANET-2012-RTD,INFECT-ERA(2013), Institut Pasteur [Paris] (IP) |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Fungal infection MESH: Trachea / diagnostic imaging Pathology Light MESH: Trachea / pathology Cryptococcus Medicine (miscellaneous) lcsh:Medicine Disease MESH: X-Ray Microtomography MESH: Cryptococcosis / diagnostic imaging Imaging MESH: Magnetic Resonance Imaging 0302 clinical medicine Immunology and Microbiology (miscellaneous) Non-invasive imaging MESH: Brain / microbiology MESH: Trachea / microbiology MESH: Animals MESH: Administration Intranasal Pathogen [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology Blood-brain barrier Mice Inbred BALB C medicine.diagnostic_test biology Brain Cryptococcosis Magnetic Resonance Imaging 3. Good health Trachea medicine.anatomical_structure Disease Progression Female MESH: Disease Progression Bioluminescence lcsh:RB1-214 medicine.medical_specialty Neuroscience (miscellaneous) MESH: Mice Inbred BALB C Blood–brain barrier General Biochemistry Genetics and Molecular Biology Mouse model 03 medical and health sciences medicine lcsh:Pathology Bioluminescence imaging Animals Resource Article MESH: Brain / diagnostic imaging Administration Intranasal Cryptococcus neoformans lcsh:R Magnetic resonance imaging X-Ray Microtomography biology.organism_classification medicine.disease MESH: Light MESH: Luminescent Measurements Disease Models Animal 030104 developmental biology Luminescent Measurements MESH: Brain / pathology MESH: Cryptococcosis / pathology Pulmonary disease MESH: Disease Models Animal MESH: Female 030217 neurology & neurosurgery MESH: Cryptococcosis / microbiology |
| Zdroj: | Disease Models & Mechanisms Disease Models & Mechanisms, Cambridge Company of Biologists, 2019, 12 (6), pp.dmm039123. ⟨10.1242/dmm.039123⟩ Disease Models & Mechanisms, 2019, 12 (6), pp.dmm039123. ⟨10.1242/dmm.039123⟩ Disease Models & Mechanisms, Vol 12, Iss 6 (2019) |
| ISSN: | 1754-8403 1754-8411 |
| Popis: | Cryptococcus neoformans is a leading cause of fungal brain infection, but the mechanism of dissemination and dynamics of cerebral infection following pulmonary disease are poorly understood. To address these questions, non-invasive techniques that can study the dynamic processes of disease development and progression in living animal models or patients are required. As such, bioluminescence imaging (BLI) has emerged as a powerful tool to evaluate the spatial and temporal distribution of infection in living animals. We aimed to study the time profile of the dissemination of cryptococcosis from the lung to the brain in murine models by engineering the first bioluminescent C. neoformans KN99α strain, expressing a sequence-optimized red-shifted luciferase. The high pathogen specificity and sensitivity of BLI was complemented by the three-dimensional anatomical information from micro-computed tomography (μCT) of the lung and magnetic resonance imaging (MRI) of the brain. These non-invasive imaging techniques provided longitudinal readouts on the spatial and temporal distribution of infection following intravenous, intranasal or endotracheal routes of inoculation. Furthermore, the imaging results correlated strongly with the fungal load in the respective organs. By obtaining dynamic and quantitative information about the extent and timing of brain infections for individual animals, we found that dissemination to the brain after primary infection of the lung is likely a late-stage event with a timeframe that is variable between animals. This novel tool in Cryptococcus research can aid the identification of host and pathogen factors involved in this process, and supports development of novel preventive or therapeutic approaches. Summary: A novel combination of bioluminescence and anatomical imaging non-invasively identified the timeframe and extent of Cryptococcus neoformans dissemination to the brain in animal models of systemic and pulmonary fungal infection. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|