The zebrafish as a novel model for the in vivo study of Toxoplasma gondii replication and interaction with macrophages
Toxoplasma gondii is an obligate intracellular parasite capable of invading any nucleated cell. Three main clonal lineages (type I, II, III) exist and murine models have driven the understanding of general and strain-specific immune mechanisms underlying Toxoplasma infection. However, murine models...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
The Company of Biologists
2020-07-01
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| Series: | Disease Models & Mechanisms |
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| Online Access: | http://dmm.biologists.org/content/13/7/dmm043091 |
| _version_ | 1818348487927922688 |
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| author | Nagisa Yoshida Marie-Charlotte Domart Christopher J. Peddie Artur Yakimovich Maria J. Mazon-Moya Thomas A. Hawkins Lucy Collinson Jason Mercer Eva-Maria Frickel Serge Mostowy |
| author_facet | Nagisa Yoshida Marie-Charlotte Domart Christopher J. Peddie Artur Yakimovich Maria J. Mazon-Moya Thomas A. Hawkins Lucy Collinson Jason Mercer Eva-Maria Frickel Serge Mostowy |
| author_sort | Nagisa Yoshida |
| collection | DOAJ |
| description | Toxoplasma gondii is an obligate intracellular parasite capable of invading any nucleated cell. Three main clonal lineages (type I, II, III) exist and murine models have driven the understanding of general and strain-specific immune mechanisms underlying Toxoplasma infection. However, murine models are limited for studying parasite-leukocyte interactions in vivo, and discrepancies exist between cellular immune responses observed in mouse versus human cells. Here, we developed a zebrafish infection model to study the innate immune response to Toxoplasma in vivo. By infecting the zebrafish hindbrain ventricle, and using high-resolution microscopy techniques coupled with computer vision-driven automated image analysis, we reveal that Toxoplasma invades brain cells and replicates inside a parasitophorous vacuole to which type I and III parasites recruit host cell mitochondria. We also show that type II and III strains maintain a higher infectious burden than type I strains. To understand how parasites are cleared in vivo, we further analyzed Toxoplasma-macrophage interactions using time-lapse microscopy and three-dimensional correlative light and electron microscopy (3D CLEM). Time-lapse microscopy revealed that macrophages are recruited to the infection site and play a key role in Toxoplasma control. High-resolution 3D CLEM revealed parasitophorous vacuole breakage in brain cells and macrophages in vivo, suggesting that cell-intrinsic mechanisms may be used to destroy the intracellular niche of tachyzoites. Together, our results demonstrate in vivo control of Toxoplasma by macrophages, and highlight the possibility that zebrafish may be further exploited as a novel model system for discoveries within the field of parasite immunity. This article has an associated First Person interview with the first author of the paper. |
| first_indexed | 2024-12-13T17:50:51Z |
| format | Article |
| id | doaj.art-1f30f192458a48f0b9a4a5258854e6b5 |
| institution | Directory Open Access Journal |
| issn | 1754-8403 1754-8411 |
| language | English |
| last_indexed | 2024-12-13T17:50:51Z |
| publishDate | 2020-07-01 |
| publisher | The Company of Biologists |
| record_format | Article |
| series | Disease Models & Mechanisms |
| spelling | doaj.art-1f30f192458a48f0b9a4a5258854e6b52022-12-21T23:36:31ZengThe Company of BiologistsDisease Models & Mechanisms1754-84031754-84112020-07-0113710.1242/dmm.043091043091The zebrafish as a novel model for the in vivo study of Toxoplasma gondii replication and interaction with macrophagesNagisa Yoshida0Marie-Charlotte Domart1Christopher J. Peddie2Artur Yakimovich3Maria J. Mazon-Moya4Thomas A. Hawkins5Lucy Collinson6Jason Mercer7Eva-Maria Frickel8Serge Mostowy9 Host-Toxoplasma Interaction Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1BF, UK Electron Microscopy Science Technology Platform, The Francis Crick Institute, 1 Midland Road, London NW1 1BF, UK Electron Microscopy Science Technology Platform, The Francis Crick Institute, 1 Midland Road, London NW1 1BF, UK MRC-Laboratory for Molecular Cell Biology, University College London, Gower Street, London, WC1E 6BT, UK Section of Microbiology, MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London SW7 2AZ, UK Department of Cell and Developmental Biology, University College London, Gower Street, London, WC1E 6BT, UK Electron Microscopy Science Technology Platform, The Francis Crick Institute, 1 Midland Road, London NW1 1BF, UK MRC-Laboratory for Molecular Cell Biology, University College London, Gower Street, London, WC1E 6BT, UK Host-Toxoplasma Interaction Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1BF, UK Section of Microbiology, MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London SW7 2AZ, UK Toxoplasma gondii is an obligate intracellular parasite capable of invading any nucleated cell. Three main clonal lineages (type I, II, III) exist and murine models have driven the understanding of general and strain-specific immune mechanisms underlying Toxoplasma infection. However, murine models are limited for studying parasite-leukocyte interactions in vivo, and discrepancies exist between cellular immune responses observed in mouse versus human cells. Here, we developed a zebrafish infection model to study the innate immune response to Toxoplasma in vivo. By infecting the zebrafish hindbrain ventricle, and using high-resolution microscopy techniques coupled with computer vision-driven automated image analysis, we reveal that Toxoplasma invades brain cells and replicates inside a parasitophorous vacuole to which type I and III parasites recruit host cell mitochondria. We also show that type II and III strains maintain a higher infectious burden than type I strains. To understand how parasites are cleared in vivo, we further analyzed Toxoplasma-macrophage interactions using time-lapse microscopy and three-dimensional correlative light and electron microscopy (3D CLEM). Time-lapse microscopy revealed that macrophages are recruited to the infection site and play a key role in Toxoplasma control. High-resolution 3D CLEM revealed parasitophorous vacuole breakage in brain cells and macrophages in vivo, suggesting that cell-intrinsic mechanisms may be used to destroy the intracellular niche of tachyzoites. Together, our results demonstrate in vivo control of Toxoplasma by macrophages, and highlight the possibility that zebrafish may be further exploited as a novel model system for discoveries within the field of parasite immunity. This article has an associated First Person interview with the first author of the paper.http://dmm.biologists.org/content/13/7/dmm043091clemin vivomacrophagestoxoplasma gondiizebrafish |
| spellingShingle | Nagisa Yoshida Marie-Charlotte Domart Christopher J. Peddie Artur Yakimovich Maria J. Mazon-Moya Thomas A. Hawkins Lucy Collinson Jason Mercer Eva-Maria Frickel Serge Mostowy The zebrafish as a novel model for the in vivo study of Toxoplasma gondii replication and interaction with macrophages Disease Models & Mechanisms clem in vivo macrophages toxoplasma gondii zebrafish |
| title | The zebrafish as a novel model for the in vivo study of Toxoplasma gondii replication and interaction with macrophages |
| title_full | The zebrafish as a novel model for the in vivo study of Toxoplasma gondii replication and interaction with macrophages |
| title_fullStr | The zebrafish as a novel model for the in vivo study of Toxoplasma gondii replication and interaction with macrophages |
| title_full_unstemmed | The zebrafish as a novel model for the in vivo study of Toxoplasma gondii replication and interaction with macrophages |
| title_short | The zebrafish as a novel model for the in vivo study of Toxoplasma gondii replication and interaction with macrophages |
| title_sort | zebrafish as a novel model for the in vivo study of toxoplasma gondii replication and interaction with macrophages |
| topic | clem in vivo macrophages toxoplasma gondii zebrafish |
| url | http://dmm.biologists.org/content/13/7/dmm043091 |
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