Abstract
Toxoplasma gondii (T. gondii), the causative agent of toxoplasmosis, is a frequent cause of brain infection. Despite its known ability to invade the brain, there is still a dire need to better understand the mechanisms by which this parasite interacts with and crosses the blood–brain barrier (BBB). The present study revealed structural and functional changes associated with infection and replication of T. gondii within human brain microvascular endothelial cells (BMECs) in vitro. T. gondii proliferated within the BMECs and disrupted the integrity of the cerebrovascular barrier through diminishing the cellular viability, disruption of the intercellular junctions and increasing permeability of the BMEC monolayer, as well as altering lipid homeostasis. Proton nuclear magnetic resonance (1H NMR)-based metabolomics combined with multivariate data analysis revealed profiles that can be attributed to infection and variations in the amounts of certain metabolites (e.g., amino acids, fatty acids) in the extracts of infected compared to control cells. Notably, treatment with the Ca2+ channel blocker verapamil rescued BMEC barrier integrity and restricted intracellular replication of the tachyzoites regardless of the time of treatment application (i.e., prior to infection, early- and late-infection). This study provides new insights into the structural and functional changes that accompany T. gondii infection of the BMECs, and sheds light upon the ability of verapamil to inhibit the parasite proliferation and to ameliorate the adverse effects caused by T. gondii infection.
Highlights
Toxoplasma gondii is an obligate intracellular apicomplexan protozoan, known to infect at least one-third of the global human population [1,2]
standard error of the mean (SEM) analysis of brain microvascular endothelial cells (BMECs) infected by tachyzoites at the early stage of infection (6 hpi), showed crescent-shaped tachyzoites in close contact with host cells (Figure 3B), with their anterior ends embedded in the intercellular space (Figure 3C)
This study showed the ability of T. gondii to invade, grow, and replicate within BMECs, and to disrupt their viability, lipid synthesis, and structural integrity, as well as induce BMEC barrier dysfunction
Summary
Toxoplasma gondii is an obligate intracellular apicomplexan protozoan, known to infect at least one-third of the global human population [1,2]. T. gondii is known to invade and proliferate within all eukaryotic cells and infect an extensive number of warm-blooded mammals. During the hematogenous dissemination of T. gondii, tachyzoites travel through the blood stream to invade tissues that are anatomically distant from the original site of infection. Once inside the brain parenchyma, T. gondii preferentially infects neuronal cells and develops persistent tissue cysts in the brain [5]. Experimental evidence indicates that T. gondii crosses the blood–brain barrier (BBB) using a ‘Trojan horse’ mechanism, breaching the BBB paracellularly by targeting tight junction proteins or crossing the BBB by direct infection of endothelial cells [6,7,8,9]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
