Morphological and biochemical repercussions ofToxoplasma gondiiinfection in a 3D human brain neurospheres model

Abstract

BackgroundToxoplasmosis is caused by the parasite Toxoplasma gondii that can infect the central nervous system (CNS), promoting neuroinflammation, neuronal loss, neurotransmitter imbalance and behavioral alterations. T. gondii infection is also related to neuropsychiatric disorders such as schizophrenia. The pathogenicity and inflammatory response in rodents are different to the case of humans, compromising the correlation between the behavioral alterations and physiological modifications observed in the disease. In the present work we used BrainSpheres, a 3D CNS model derived from human pluripotent stem cells (iPSC), to investigate the morphological and biochemical repercussions of T. gondii infection in human neural cells.MethodsWe evaluated T. gondii ME49 strain proliferation and cyst formation in both 2D cultured human neural cells and BrainSpheres. Aspects of cell morphology, ultrastructure, viability, gene expression of neural phenotype markers, as well as secretion of inflammatory mediators were evaluated for 2 and 4 weeks post infection in BrainSpheres.ResultsT. gondii can infect BrainSpheres, proliferating and inducing cysts formation, neural cell death, alteration in neural gene expression and triggering the release of several inflammatory mediator.ConclusionsBrainSpheres reproduce many aspects of T. gondii infection in human CNS, constituting a useful model to study the neurotoxicity and neuroinflammation mediated by the parasite. In addition, BrainSpheres can be an important tool for better understanding the possible correlation between psychiatric disorders and human CNS infection with T. gondii

Innate immune cell response to host-parasite interaction in a human intestinal tissue microphysiological system

“…Organoid technologies enable the expansion of primary intestinal stem cells and are regarded as a powerful in vitro tool for modeling intestinal epithelial tissue due to their structural and functional resemblance to in vivo tissue ( 49 , 50 ). Several studies have used these techniques to study T. gondii infection in intestinal organoids ( 51 ) as well and in organoid models of the brain and central nervous systems ( 52 , 53 ). While apical access can sometimes be limited when using these techniques, methods to form epithelial monolayers from intestinal organoid fragments have been reported ( 54 , 55 ), where the major epithelial cell types found in 3D organoids are retained when cultured on hard surfaces coated with Matrigel or collagen ( 56 ).…”