Toxoplasma gondii tachyzoites cross retinal endothelium assisted by intercellular adhesion molecule‐1 in vitro

Abstract

Retinal infection is the most common clinical manifestation of toxoplasmosis. The route by which circulating Toxoplasma gondii tachyzoites cross the vascular endothelium to enter the human retina is unknown. Convincing studies using murine encephalitis models have strongly implicated leukocyte taxis as one pathway used by the parasite to access target organs. To establish whether tachyzoites might also interact directly with vascular endothelium, we populated a transwell system with human ocular endothelial cells. Human retinal endothelial monolayers permitted transmigration of tachyzoites of RH and three natural isolate strains. Antibody blockade of intercellular adhesion molecule-1 significantly reduced this migration, but did not impact tachyzoite movement across an endothelial monolayer derived from the choroid, which lies adjacent to the retina within the eye. In demonstrating that tachyzoites are capable of independent migration across human vascular endothelium in vitro, this study carries implications for the development of therapeutics aimed at preventing access of tachyzoites to the retina.

From the blood to the brain: avenues of eukaryotic pathogen dissemination to the central nervous system

“…Extracellular T. gondii tachyzoites can adhere to human vascular endothelium in conditions of shear stress by using the parasite adhesin MIC2 [7]. After adhesion, tachyzoites may either transmigrate across the endothelial barrier [8] or invade endothelial cells [9], and invasion appears to predominate [7]. Interestingly, human brain endothelial cells are more permissive to T. gondii replication than neurons or microglia [10].…”

“…Infection enhances the expression of the host adhesion molecules ICAM-1, VCAM-1, and ALCAM in the CNS [6,12]. In particular, ICAM-1 interacts with MIC2 to facilitate the migration of extracellular tachyzoites across epithelium [13] and retinal endothelium [8] without disrupting monolayer integrity.…”

Intraocular Cysts ofToxoplasma gondiiin Patients with Necrotizing Retinitis following Periocular/Intraocular Triamcinolone Injection

“…An in vitro study has demonstrated that tachyzoites are capable of independent migration across human vascular endothelium. 8 Our patients had been extensively treated with local (periocular/intravitreal) and oral corticosteroids that triggered widespread retinal necrosis facilitating the growth and migration of toxoplasma parasites leading to their subsequent detection on cytology of subretinal and vitreous aspirates. In the first case, failure to detect them in the vitreous aspirate or retinal tissue highlights the difficulty in detecting these organisms on cytology of intraocular samples.…”

Possible Pivotal Role of Latent Chronic T. gondii Infection in the Pathogenesis of Atherosclerosis

“…superfamily member) in vitro, and ICAM-1 blockade significantly (by approximately 50%, p < 0.001) inhibited the parasite migration across stimulated human retinal, but not choroidal, vascular endothelium [63] . There has been interest in the heterogeneity of vascular endothelium, not only between arteries and venous types [64] , but also between same type vessels located within different organs or within different tissues in the same organ [65,66] .…”

“…Smith et al [62] found that retinal vascular endothelium cells have enhanced susceptibility to infection with T. gondii tachyzoites in comparison with aorta (55% more), umbilical vein (33%), and dermal endothelial cells (34% more), and tropism of different pathogens for particular cell types and/or specific tissue sites was a long-recognized biological phenomenon [62] . Free T. gondii tachyzoites had the ability to transmigrate a stimulated human retinal endothelium monolayer [63] . Tachyzoites crossed retinal endothelium assisted by intercellular adhesion molecule-1 (ICAM-1) (the cell surface IgG immunoglobin [43] ; with own modification).…”