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Concomitant Isolation of Primary Astrocytes and Microglia for Protozoa Parasite Infection
Published on: March 18, 2020
Cryptococcus neoformans-astrocyte interactions: effect on fungal blood brain barrier disruption, brain invasion, and
Yeon Hwa Woo1, Luis R Martinez2
1Department of Metallurgical, Materials and Biomedical Engineering, College of Engineering, The University of Texas at El Paso, El Paso, TX, USA.
Abstract:
Cryptococcus neoformans is an opportunistic, neurotropic, and encapsulated fungus that causes life-threatening cryptococcal meningitis (CM), especially in regions of the world where AIDS is endemic. The polysaccharide capsule of C. neoformans is the fungus major virulent factor, being copiously released during infection and causing immunosuppressive defects in the host. Although the capsular material is commonly associated with reactive astrocytes in fatal CM, little is known about the molecular and cellular interactions among astroglia and C. neoformans. As astrocytes also make up the neurovascular unit at the blood-brain barrier (BBB), which C. neoformans must transverse to colonize the central nervous system and cause CM; these cells may play a significant regulatory role in the prevention and progression of infection. For example, astrocytes are implicated in neurological disease including the regulation of cerebral intracranial pressure, immune function, and water homeostasis. Hence, in this review, we provide a general overview of astroglia biology and discuss the current knowledge on C. neoformans-astrocyte interactions including their involvement in the development of CM. This "gliocentric view" of cerebral cryptococcosis suggests that therapeutic interventions particularly targeting at preserving the neuroprotective function of astrocytes may be used in preventing and managing C. neoformans BBB transmigration, brain invasion, colonization, and meningitis.
Insights
Cryptococcus neoformans causes meningitis, especially in AIDS patients. This review explores how astrocytes interact with the fungus, offering potential new therapeutic targets to prevent brain invasion.
Area of Science:
- Neuroscience
- Mycology
- Immunology
Background:
- Cryptococcus neoformans is an opportunistic fungus causing life-threatening cryptococcal meningitis (CM), particularly in AIDS patients.
- The fungal capsule is a key virulence factor, contributing to immunosuppression.
- Astrocytes, crucial components of the blood-brain barrier (BBB), are implicated in CM pathogenesis, yet their interactions with C. neoformans are poorly understood.
Purpose of the Study:
- To review astroglia biology and C. neoformans-astrocyte interactions.
- To highlight the role of astrocytes in the development of CM.
- To propose a gliocentric approach for therapeutic interventions.
Main Methods:
- Literature review of existing research on C. neoformans, astrocytes, and CM.
- Synthesis of current knowledge on fungal-glial interactions in the central nervous system.
- Analysis of astrocyte functions in neuroprotection and BBB integrity.
Main Results:
- Astrocytes are involved in regulating intracranial pressure, immune function, and water homeostasis.
- C. neoformans interacts with astrocytes at the BBB, influencing fungal transmigration and CNS invasion.
- Reactive astrocytes are observed in fatal CM cases, suggesting their involvement.
Conclusions:
- Astrocytes play a significant regulatory role in preventing and progressing C. neoformans CNS infection.
- A gliocentric therapeutic strategy targeting astrocyte neuroprotective functions may prevent BBB transmigration, brain invasion, and meningitis.
- Understanding C. neoformans-astrocyte interactions is crucial for managing cerebral cryptococcosis.

