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bioRxiv · 10.1101/378588

Radial Glia cell infection by Toxoplasma gondii disrupts brain microvascular endothelial cell integrity

Adesse, D.·Marcos, A. C.·Siqueira, M.·Cascabulho, C. M.·Waghabi, M. C.·Barbosa, H. S.·Stipursky, J.
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Abstract

Congenital toxoplasmosis is a parasitic disease that occurs due vertical transmission of the protozoan Toxoplasma gondii (T. gondii) during pregnancy. The parasite crosses the placental barrier and reaches the developing brain, infecting progenitor, glial, neuronal and vascular cell types. Although the role of Radial glia (RG) neural stem cells in the development of the brain vasculature has been recently investigated, the impact of T. gondii infection in these events is not yet understood. Herein, we studied the role of T. gondii infection on RG cell function and its interaction with endothelial cells. By infecting isolated RG cells with T. gondii tachyzoites, we observed reduced cell proliferation and neurogenesis without affecting gliogenesis levels. Conditioned medium (CM) from RG control cultures increased ZO-1 and {beta}-catenin protein levels and organization on endothelial bEnd.3 cells membranes, which was completely impaired by CM from infected RG, resulting in decreased transendothelial electrical resistance (TEER). Cytokine Bead Array and ELISA assays revealed the presence of increased levels of the pro-inflammatory cytokine IL-6 and reduced levels of anti-inflammatory cytokine TGF-{beta}1 in CM from T.gondii-infected RG cells. Treatment with recombinant TGF-{beta}1 concomitantly with CM from infected RG cultures led to restoration of ZO-1 staining in bEnd.3 cells. Our results suggest that infection of RG cells by T. gondii modulate cytokine secretion, which might contribute to endothelial loss of barrier properties, thus leading to impairment of neurovascular interaction establishment.

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Adesse, D., Marcos, A. C., Siqueira, M., Cascabulho, C. M., Waghabi, M. C., Barbosa, H. S., Stipursky, J.. 2018-07-27. Radial Glia cell infection by Toxoplasma gondii disrupts brain microvascular endothelial cell integrity. https://doi.org/10.1101/378588

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