Infection with Toxoplasma gondii triggers coagulation at the blood-brain barrier and a reduction in cerebral blood flow
Abstract 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...
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BMC
2025-01-01
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| Series: | Journal of Neuroinflammation |
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| Online Access: | https://doi.org/10.1186/s12974-024-03330-1 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Evelyn M. Hoover |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-76d1b180a1f84ccfb54a476075a4d62e |
| institution | Kabale University |
| issn | 1742-2094 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neuroinflammation |
| spelling | doaj-art-76d1b180a1f84ccfb54a476075a4d62e2025-01-12T12:33:30ZengBMCJournal of Neuroinflammation1742-20942025-01-0122111710.1186/s12974-024-03330-1Infection with Toxoplasma gondii triggers coagulation at the blood-brain barrier and a reduction in cerebral blood flowEvelyn M. Hoover0Christine A. Schneider1Christian Crouzet2Tatiane S. Lima3Dario X. Figueroa Velez4Cuong J. Tran5Dritan Agalliu6Sunil P. Gandhi7Bernard Choi8Melissa B. Lodoen9Department of Molecular Biology and Biochemistry, University of California IrvineDepartment of Molecular Biology and Biochemistry, University of California IrvineDepartment of Biomedical Engineering, University of California IrvineDepartment of Biological Sciences, California State Polytechnic UniversityDepartment of Neurobiology and Behavior, University of California IrvineDepartment of Molecular Biology and Biochemistry, University of California IrvineDepartment of Pathology and Cell Biology, Columbia University Irving Medical CenterDepartment of Neurobiology and Behavior, University of California IrvineDepartment of Biomedical Engineering, University of California IrvineDepartment of Molecular Biology and Biochemistry, University of California IrvineAbstract 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.https://doi.org/10.1186/s12974-024-03330-1Toxoplasma gondiiCNS infectionThrombosisCerebral blood flowBlood-brain barrier |
| spellingShingle | 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 Infection with Toxoplasma gondii triggers coagulation at the blood-brain barrier and a reduction in cerebral blood flow Journal of Neuroinflammation Toxoplasma gondii CNS infection Thrombosis Cerebral blood flow Blood-brain barrier |
| title | Infection with Toxoplasma gondii triggers coagulation at the blood-brain barrier and a reduction in cerebral blood flow |
| title_full | Infection with Toxoplasma gondii triggers coagulation at the blood-brain barrier and a reduction in cerebral blood flow |
| title_fullStr | Infection with Toxoplasma gondii triggers coagulation at the blood-brain barrier and a reduction in cerebral blood flow |
| title_full_unstemmed | Infection with Toxoplasma gondii triggers coagulation at the blood-brain barrier and a reduction in cerebral blood flow |
| title_short | Infection with Toxoplasma gondii triggers coagulation at the blood-brain barrier and a reduction in cerebral blood flow |
| title_sort | infection with toxoplasma gondii triggers coagulation at the blood brain barrier and a reduction in cerebral blood flow |
| topic | Toxoplasma gondii CNS infection Thrombosis Cerebral blood flow Blood-brain barrier |
| url | https://doi.org/10.1186/s12974-024-03330-1 |
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