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Background <p>Immunothrombosis is the process by which the coagulation cascade interacts with the innate immune system to control infection. However, the formation of clots within the brain vasculature can be detrimental to the host. Recent work has demonstrated that <i>Toxoplasma gondii</i> infects and lyses central nervous system (CNS) endothelial cells that form the blood-brain barrier (BBB). However, little is known about the effect of <i>T. gondii</i> infection on the BBB and the functional consequences of infection on cerebral blood flow (CBF) during the different stages of infection.</p> Main body <p>We demonstrate that brain endothelial cells upregulate the adhesion molecules ICAM-1 and VCAM-1 and become morphologically more tortuous during acute <i>T. gondii</i> infection of mice. Longitudinal two-photon imaging of cerebral blood vessels during infection in mice revealed vascular occlusion in the brain, prompting an analysis of the coagulation cascade. We detected platelet-fibrin clots within the cerebral vasculature during acute infection. Analysis of CBF using longitudinal laser-speckle imaging during <i>T. gondii</i> infection demonstrated that CBF decreased during acute infection, recovered during stable chronic infection, and decreased again during reactivation of the infection induced by IFN-γ depletion. Finally, we demonstrate that treatment of mice with a low-molecular-weight heparin, an anticoagulant, during infection partially rescued CBF in <i>T. gondii</i>-infected mice without affecting parasite burden.</p> Conclusions <p>Our data provide insight into the host-pathogen interactions of a CNS parasite within the brain vasculature and suggest that thrombosis and changes in cerebral hemodynamics may be an unappreciated aspect of infection with <i>T. gondii</i>.</p>

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Infection with Toxoplasma gondii triggers coagulation at the blood-brain barrier and a reduction in cerebral blood flow

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年1月8日

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  • Evelyn M. Hoover,
  • Christine A. Schneider,
  • Christian Crouzet,
  • Tatiane S. Lima,
  • Dario X. Figueroa Velez,
  • Cuong J. Tran,
  • Dritan Agalliu,
  • Sunil P. Gandhi,
  • Bernard Choi,
  • Melissa B. Lodoen

摘要

Background

Immunothrombosis is the process by which the coagulation cascade interacts with the innate immune system to control infection. However, the formation of clots within the brain vasculature can be detrimental to the host. Recent work has demonstrated that Toxoplasma gondii infects and lyses central nervous system (CNS) endothelial cells that form the blood-brain barrier (BBB). However, little is known about the effect of T. gondii infection on the BBB and the functional consequences of infection on cerebral blood flow (CBF) during the different stages of infection.

Main body

We demonstrate that brain endothelial cells upregulate the adhesion molecules ICAM-1 and VCAM-1 and become morphologically more tortuous during acute T. gondii infection of mice. Longitudinal two-photon imaging of cerebral blood vessels during infection in mice revealed vascular occlusion in the brain, prompting an analysis of the coagulation cascade. We detected platelet-fibrin clots within the cerebral vasculature during acute infection. Analysis of CBF using longitudinal laser-speckle imaging during T. gondii infection demonstrated that CBF decreased during acute infection, recovered during stable chronic infection, and decreased again during reactivation of the infection induced by IFN-γ depletion. Finally, we demonstrate that treatment of mice with a low-molecular-weight heparin, an anticoagulant, during infection partially rescued CBF in T. gondii-infected mice without affecting parasite burden.

Conclusions

Our data provide insight into the host-pathogen interactions of a CNS parasite within the brain vasculature and suggest that thrombosis and changes in cerebral hemodynamics may be an unappreciated aspect of infection with T. gondii.