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Primary brain cell infection by Toxoplasma gondii reveals the extent and dynamics of parasite differentiation and its impact on neuron biology
Toxoplasma gondii is a eukaryotic parasite that forms latent cysts in the brain of immunocompetent individuals. The latent parasite infection of the immune-privileged central nervous system is linked to most complications. With no drug currently available to eliminate the latent cysts in the brain o...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Royal Society
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8492179/ https://www.ncbi.nlm.nih.gov/pubmed/34610266 http://dx.doi.org/10.1098/rsob.210053 |
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author | Mouveaux, Thomas Roger, Emmanuel Gueye, Alioune Eysert, Fanny Huot, Ludovic Grenier-Boley, Benjamin Lambert, Jean-Charles Gissot, Mathieu |
author_facet | Mouveaux, Thomas Roger, Emmanuel Gueye, Alioune Eysert, Fanny Huot, Ludovic Grenier-Boley, Benjamin Lambert, Jean-Charles Gissot, Mathieu |
author_sort | Mouveaux, Thomas |
collection | PubMed |
description | Toxoplasma gondii is a eukaryotic parasite that forms latent cysts in the brain of immunocompetent individuals. The latent parasite infection of the immune-privileged central nervous system is linked to most complications. With no drug currently available to eliminate the latent cysts in the brain of infected hosts, the consequences of neurons' long-term infection are unknown. It has long been known that T. gondii specifically differentiates into a latent form (bradyzoite) in neurons, but how the infected neuron responds to the infection remains to be elucidated. We have established a new in vitro model resulting in the production of mature bradyzoite cysts in brain cells. Using dual, host and parasite RNA-seq, we characterized the dynamics of differentiation of the parasite, revealing the involvement of key pathways in this process. Moreover, we identified how the infected brain cells responded to the parasite infection revealing the drastic changes that take place. We showed that neuronal-specific pathways are strongly affected, with synapse signalling being particularly affected, especially glutamatergic synapse signalling. The establishment of this new in vitro model allows investigating both the dynamics of parasite differentiation and the specific response of neurons to long-term infection by this parasite. |
format | Online Article Text |
id | pubmed-8492179 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | The Royal Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-84921792021-10-29 Primary brain cell infection by Toxoplasma gondii reveals the extent and dynamics of parasite differentiation and its impact on neuron biology Mouveaux, Thomas Roger, Emmanuel Gueye, Alioune Eysert, Fanny Huot, Ludovic Grenier-Boley, Benjamin Lambert, Jean-Charles Gissot, Mathieu Open Biol Research Toxoplasma gondii is a eukaryotic parasite that forms latent cysts in the brain of immunocompetent individuals. The latent parasite infection of the immune-privileged central nervous system is linked to most complications. With no drug currently available to eliminate the latent cysts in the brain of infected hosts, the consequences of neurons' long-term infection are unknown. It has long been known that T. gondii specifically differentiates into a latent form (bradyzoite) in neurons, but how the infected neuron responds to the infection remains to be elucidated. We have established a new in vitro model resulting in the production of mature bradyzoite cysts in brain cells. Using dual, host and parasite RNA-seq, we characterized the dynamics of differentiation of the parasite, revealing the involvement of key pathways in this process. Moreover, we identified how the infected brain cells responded to the parasite infection revealing the drastic changes that take place. We showed that neuronal-specific pathways are strongly affected, with synapse signalling being particularly affected, especially glutamatergic synapse signalling. The establishment of this new in vitro model allows investigating both the dynamics of parasite differentiation and the specific response of neurons to long-term infection by this parasite. The Royal Society 2021-10-06 /pmc/articles/PMC8492179/ /pubmed/34610266 http://dx.doi.org/10.1098/rsob.210053 Text en © 2021 The Authors. https://creativecommons.org/licenses/by/4.0/Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, provided the original author and source are credited. |
spellingShingle | Research Mouveaux, Thomas Roger, Emmanuel Gueye, Alioune Eysert, Fanny Huot, Ludovic Grenier-Boley, Benjamin Lambert, Jean-Charles Gissot, Mathieu Primary brain cell infection by Toxoplasma gondii reveals the extent and dynamics of parasite differentiation and its impact on neuron biology |
title | Primary brain cell infection by Toxoplasma gondii reveals the extent and dynamics of parasite differentiation and its impact on neuron biology |
title_full | Primary brain cell infection by Toxoplasma gondii reveals the extent and dynamics of parasite differentiation and its impact on neuron biology |
title_fullStr | Primary brain cell infection by Toxoplasma gondii reveals the extent and dynamics of parasite differentiation and its impact on neuron biology |
title_full_unstemmed | Primary brain cell infection by Toxoplasma gondii reveals the extent and dynamics of parasite differentiation and its impact on neuron biology |
title_short | Primary brain cell infection by Toxoplasma gondii reveals the extent and dynamics of parasite differentiation and its impact on neuron biology |
title_sort | primary brain cell infection by toxoplasma gondii reveals the extent and dynamics of parasite differentiation and its impact on neuron biology |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8492179/ https://www.ncbi.nlm.nih.gov/pubmed/34610266 http://dx.doi.org/10.1098/rsob.210053 |
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