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Shear Forces Enhance Toxoplasma gondii Tachyzoite Motility on Vascular Endothelium

Toxoplasma gondii is a highly successful parasite that infects approximately one-third of the human population and can cause fatal disease in immunocompromised individuals. Systemic parasite dissemination to organs such as the brain and eye is critical to pathogenesis. T. gondii can disseminate via...

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Autores principales: Harker, Katherine S., Jivan, Elizabeth, McWhorter, Frances Y., Liu, Wendy F., Lodoen, Melissa B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Microbiology 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3977363/
https://www.ncbi.nlm.nih.gov/pubmed/24692639
http://dx.doi.org/10.1128/mBio.01111-13
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author Harker, Katherine S.
Jivan, Elizabeth
McWhorter, Frances Y.
Liu, Wendy F.
Lodoen, Melissa B.
author_facet Harker, Katherine S.
Jivan, Elizabeth
McWhorter, Frances Y.
Liu, Wendy F.
Lodoen, Melissa B.
author_sort Harker, Katherine S.
collection PubMed
description Toxoplasma gondii is a highly successful parasite that infects approximately one-third of the human population and can cause fatal disease in immunocompromised individuals. Systemic parasite dissemination to organs such as the brain and eye is critical to pathogenesis. T. gondii can disseminate via the circulation, and both intracellular and extracellular modes of transport have been proposed. However, the processes by which extracellular tachyzoites adhere to and migrate across vascular endothelium under the conditions of rapidly flowing blood remain unknown. We used microfluidics and time-lapse fluorescence microscopy to examine the interactions between extracellular T. gondii and primary human endothelial cells under conditions of physiologic shear stress. Remarkably, tachyzoites adhered to and glided on human vascular endothelium under shear stress conditions. Compared to static conditions, shear stress enhanced T. gondii helical gliding, resulting in a significantly greater displacement, and increased the percentage of tachyzoites that invaded or migrated across the endothelium. The intensity of the shear forces (from 0.5 to 10 dynes/cm(2)) influenced both initial and sustained adhesion to endothelium. By examining tachyzoites deficient in the T. gondii adhesion protein MIC2, we found that MIC2 contributed to initial adhesion but was not required for adhesion strengthening. These data suggest that under fluidic conditions, T. gondii adhesion to endothelium may be mediated by a multistep cascade of interactions that is governed by unique combinations of adhesion molecules. This work provides novel information about tachyzoite interactions with vascular endothelium and contributes to our understanding of T. gondii dissemination in the infected host.
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spelling pubmed-39773632014-04-09 Shear Forces Enhance Toxoplasma gondii Tachyzoite Motility on Vascular Endothelium Harker, Katherine S. Jivan, Elizabeth McWhorter, Frances Y. Liu, Wendy F. Lodoen, Melissa B. mBio Research Article Toxoplasma gondii is a highly successful parasite that infects approximately one-third of the human population and can cause fatal disease in immunocompromised individuals. Systemic parasite dissemination to organs such as the brain and eye is critical to pathogenesis. T. gondii can disseminate via the circulation, and both intracellular and extracellular modes of transport have been proposed. However, the processes by which extracellular tachyzoites adhere to and migrate across vascular endothelium under the conditions of rapidly flowing blood remain unknown. We used microfluidics and time-lapse fluorescence microscopy to examine the interactions between extracellular T. gondii and primary human endothelial cells under conditions of physiologic shear stress. Remarkably, tachyzoites adhered to and glided on human vascular endothelium under shear stress conditions. Compared to static conditions, shear stress enhanced T. gondii helical gliding, resulting in a significantly greater displacement, and increased the percentage of tachyzoites that invaded or migrated across the endothelium. The intensity of the shear forces (from 0.5 to 10 dynes/cm(2)) influenced both initial and sustained adhesion to endothelium. By examining tachyzoites deficient in the T. gondii adhesion protein MIC2, we found that MIC2 contributed to initial adhesion but was not required for adhesion strengthening. These data suggest that under fluidic conditions, T. gondii adhesion to endothelium may be mediated by a multistep cascade of interactions that is governed by unique combinations of adhesion molecules. This work provides novel information about tachyzoite interactions with vascular endothelium and contributes to our understanding of T. gondii dissemination in the infected host. American Society of Microbiology 2014-04-01 /pmc/articles/PMC3977363/ /pubmed/24692639 http://dx.doi.org/10.1128/mBio.01111-13 Text en Copyright © 2014 Harker et al. http://creativecommons.org/licenses/by-nc-sa/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-ShareAlike 3.0 Unported license (http://creativecommons.org/licenses/by-nc-sa/3.0/) , which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Harker, Katherine S.
Jivan, Elizabeth
McWhorter, Frances Y.
Liu, Wendy F.
Lodoen, Melissa B.
Shear Forces Enhance Toxoplasma gondii Tachyzoite Motility on Vascular Endothelium
title Shear Forces Enhance Toxoplasma gondii Tachyzoite Motility on Vascular Endothelium
title_full Shear Forces Enhance Toxoplasma gondii Tachyzoite Motility on Vascular Endothelium
title_fullStr Shear Forces Enhance Toxoplasma gondii Tachyzoite Motility on Vascular Endothelium
title_full_unstemmed Shear Forces Enhance Toxoplasma gondii Tachyzoite Motility on Vascular Endothelium
title_short Shear Forces Enhance Toxoplasma gondii Tachyzoite Motility on Vascular Endothelium
title_sort shear forces enhance toxoplasma gondii tachyzoite motility on vascular endothelium
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3977363/
https://www.ncbi.nlm.nih.gov/pubmed/24692639
http://dx.doi.org/10.1128/mBio.01111-13
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