The zebrafish as a novel model for the in vivo study of Toxoplasma gondii replication and interaction with macrophages.

Autor:	Yoshida N; 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.; Department of Infection Biology, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK., Domart MC; Electron Microscopy Science Technology Platform, The Francis Crick Institute, 1 Midland Road, London NW1 1BF, UK., Peddie CJ; Electron Microscopy Science Technology Platform, The Francis Crick Institute, 1 Midland Road, London NW1 1BF, UK., Yakimovich A; MRC-Laboratory for Molecular Cell Biology, University College London, Gower Street, London, WC1E 6BT, UK.; Artificial Intelligence for Life Sciences CIC, 40 Gowers Walk, London, E1 8BH, UK., Mazon-Moya MJ; Section of Microbiology, MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London SW7 2AZ, UK., Hawkins TA; Department of Cell and Developmental Biology, University College London, Gower Street, London, WC1E 6BT, UK., Collinson L; Electron Microscopy Science Technology Platform, The Francis Crick Institute, 1 Midland Road, London NW1 1BF, UK., Mercer J; MRC-Laboratory for Molecular Cell Biology, University College London, Gower Street, London, WC1E 6BT, UK.; Institute of Microbiology and Infection, School of Biosciences, University of Birmingham, Edgbaston, B15 2TT, UK., Frickel EM; Host-Toxoplasma Interaction Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1BF, UK serge.mostowy@lshtm.ac.uk e.frickel@bham.ac.uk.; Institute of Microbiology and Infection, School of Biosciences, University of Birmingham, Edgbaston, B15 2TT, UK., Mostowy S; Section of Microbiology, MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London SW7 2AZ, UK serge.mostowy@lshtm.ac.uk e.frickel@bham.ac.uk.; Department of Infection Biology, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK.
Jazyk:	angličtina
Zdroj:	Disease models & mechanisms [Dis Model Mech] 2020 Jul 20; Vol. 13 (7). Date of Electronic Publication: 2020 Jul 20.
DOI:	10.1242/dmm.043091
Abstrakt:	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. Competing Interests: Competing interestsThe authors declare no competing or financial interests. (© 2020. Published by The Company of Biologists Ltd.)
Databáze:	MEDLINE
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