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An In Vitro Brain Endothelial Model for Studies of Cryptococcal Transmigration into the Central Nervous System
Felipe H Santiago-Tirado1,2, Robyn S Klein3, Tamara L Doering1
1Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri.
Abstract:
Cryptococcus neoformans is an environmental yeast found worldwide that causes lethal brain infections, particularly in immunocompromised hosts. In 2016, there were 280,000 cases of cryptococcal meningitis in the HIV+ population, two-thirds of them fatal; other immunocompromised patients are also affected. The burden of cryptococcal disease and the limits of current chemotherapy create a pressing need for improved treatment. One hindrance to the development of new therapies is lack of understanding of how this pathogen breaches the barriers protecting the brain. Here we describe a tool for investigating this process. This simple in vitro blood-brain-barrier (BBB) model, based on a human brain endothelial cell line grown on a permeable membrane, may be used to assay the BBB transmigration of C. neoformans or other neurotropic pathogens. © 2019 by John Wiley & Sons, Inc.
Insights
A new in vitro model using human brain endothelial cells helps researchers study how Cryptococcus neoformans, a yeast causing deadly brain infections, crosses the blood-brain barrier (BBB). This tool aids in developing better treatments for cryptococcal meningitis.
Area of Science:
- * Infectious Diseases
- * Neuroscience
- * Microbiology
Background:
- * Cryptococcus neoformans causes fatal cryptococcal meningitis, especially in HIV+ individuals.
- * Limited understanding of pathogen brain entry hinders new therapeutic development.
- * Current chemotherapy for cryptococcal infections has limitations.
Purpose of the Study:
- * To develop a tool for investigating how Cryptococcus neoformans breaches the blood-brain barrier (BBB).
- * To provide a model for studying neurotropic pathogen transmigration.
Main Methods:
- * Development of a simple in vitro blood-brain barrier (BBB) model.
- * Utilized a human brain endothelial cell line grown on a permeable membrane.
Main Results:
- * The study presents a novel in vitro BBB model.
- * This model can be used to assay the transmigration of C. neoformans.
Conclusions:
- * The developed in vitro BBB model is a valuable tool for studying C. neoformans brain invasion.
- * Facilitates research into mechanisms of neurotropic pathogen entry and potential therapeutic targets.
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