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Toxoplasma gondii Dissemination in the Brain Is Facilitated by Infiltrating Peripheral Immune Cells

Despite recent advances in our understanding of pathogenic access to the central nervous system (CNS), the mechanisms by which intracellular pathogens disseminate within the dense cellular network of neural tissue remain poorly understood. To address this issue, longitudinal analysis of Toxoplasma g...

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Autores principales: Schneider, Christine A., Figueroa Velez, Dario X., Orchanian, Stephanie B., Shallberg, Lindsey A., Agalliu, Dritan, Hunter, Christopher A., Gandhi, Sunil P., Lodoen, Melissa B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9765297/
https://www.ncbi.nlm.nih.gov/pubmed/36445695
http://dx.doi.org/10.1128/mbio.02838-22
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author Schneider, Christine A.
Figueroa Velez, Dario X.
Orchanian, Stephanie B.
Shallberg, Lindsey A.
Agalliu, Dritan
Hunter, Christopher A.
Gandhi, Sunil P.
Lodoen, Melissa B.
author_facet Schneider, Christine A.
Figueroa Velez, Dario X.
Orchanian, Stephanie B.
Shallberg, Lindsey A.
Agalliu, Dritan
Hunter, Christopher A.
Gandhi, Sunil P.
Lodoen, Melissa B.
author_sort Schneider, Christine A.
collection PubMed
description Despite recent advances in our understanding of pathogenic access to the central nervous system (CNS), the mechanisms by which intracellular pathogens disseminate within the dense cellular network of neural tissue remain poorly understood. To address this issue, longitudinal analysis of Toxoplasma gondii dissemination in the brain was conducted using 2-photon imaging through a cranial window in living mice that transgenically express enhanced green fluorescent protein (eGFP)-claudin-5. Extracellular T. gondii parasites were observed migrating slowly (1.37 ± 1.28 μm/min) and with low displacement within the brain. In contrast, a population of highly motile infected cells transported vacuoles of T. gondii significantly faster (6.30 ± 3.09 μm/min) and with a higher displacement than free parasites. Detailed analysis of microglial dynamics using CX3CR1-GFP mice revealed that T. gondii-infected microglia remained stationary, and infection did not increase the extension/retraction of microglial processes. The role of infiltrating immune cells in shuttling T. gondii was examined by labeling of peripheral hematopoietic cells with anti-CD45 antibody. Infected CD45(+) cells were found crawling along the CNS vessel walls and trafficked T. gondii within the brain parenchyma at significantly higher speeds (3.35 ± 1.70 μm/min) than extracellular tachyzoites. Collectively, these findings highlight a dual role for immune cells in neuroprotection and in facilitating parasite dissemination within the brain.
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spelling pubmed-97652972022-12-21 Toxoplasma gondii Dissemination in the Brain Is Facilitated by Infiltrating Peripheral Immune Cells Schneider, Christine A. Figueroa Velez, Dario X. Orchanian, Stephanie B. Shallberg, Lindsey A. Agalliu, Dritan Hunter, Christopher A. Gandhi, Sunil P. Lodoen, Melissa B. mBio Research Article Despite recent advances in our understanding of pathogenic access to the central nervous system (CNS), the mechanisms by which intracellular pathogens disseminate within the dense cellular network of neural tissue remain poorly understood. To address this issue, longitudinal analysis of Toxoplasma gondii dissemination in the brain was conducted using 2-photon imaging through a cranial window in living mice that transgenically express enhanced green fluorescent protein (eGFP)-claudin-5. Extracellular T. gondii parasites were observed migrating slowly (1.37 ± 1.28 μm/min) and with low displacement within the brain. In contrast, a population of highly motile infected cells transported vacuoles of T. gondii significantly faster (6.30 ± 3.09 μm/min) and with a higher displacement than free parasites. Detailed analysis of microglial dynamics using CX3CR1-GFP mice revealed that T. gondii-infected microglia remained stationary, and infection did not increase the extension/retraction of microglial processes. The role of infiltrating immune cells in shuttling T. gondii was examined by labeling of peripheral hematopoietic cells with anti-CD45 antibody. Infected CD45(+) cells were found crawling along the CNS vessel walls and trafficked T. gondii within the brain parenchyma at significantly higher speeds (3.35 ± 1.70 μm/min) than extracellular tachyzoites. Collectively, these findings highlight a dual role for immune cells in neuroprotection and in facilitating parasite dissemination within the brain. American Society for Microbiology 2022-11-29 /pmc/articles/PMC9765297/ /pubmed/36445695 http://dx.doi.org/10.1128/mbio.02838-22 Text en Copyright © 2022 Schneider et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Schneider, Christine A.
Figueroa Velez, Dario X.
Orchanian, Stephanie B.
Shallberg, Lindsey A.
Agalliu, Dritan
Hunter, Christopher A.
Gandhi, Sunil P.
Lodoen, Melissa B.
Toxoplasma gondii Dissemination in the Brain Is Facilitated by Infiltrating Peripheral Immune Cells
title Toxoplasma gondii Dissemination in the Brain Is Facilitated by Infiltrating Peripheral Immune Cells
title_full Toxoplasma gondii Dissemination in the Brain Is Facilitated by Infiltrating Peripheral Immune Cells
title_fullStr Toxoplasma gondii Dissemination in the Brain Is Facilitated by Infiltrating Peripheral Immune Cells
title_full_unstemmed Toxoplasma gondii Dissemination in the Brain Is Facilitated by Infiltrating Peripheral Immune Cells
title_short Toxoplasma gondii Dissemination in the Brain Is Facilitated by Infiltrating Peripheral Immune Cells
title_sort toxoplasma gondii dissemination in the brain is facilitated by infiltrating peripheral immune cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9765297/
https://www.ncbi.nlm.nih.gov/pubmed/36445695
http://dx.doi.org/10.1128/mbio.02838-22
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