Capsule structure changes associated with Cryptococcus neoformans crossing of the blood-brain barrier
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Updated: Aug 19, 2026

Automated Measurement of Cryptococcal Species Polysaccharide Capsule and Cell Body
Published on: January 11, 2018
Caroline Charlier1, Fabrice Chrétien, Marielle Baudrimont
1Unité de Mycologie Moléculaire, CNRS FRE2948, Institut Pasteur, 25 rue du Dr. Roux, 75724 Paris cedex 15, France.
Abstract:
Cryptococcus neoformans is a yeast responsible for disseminated meningoencephalitis in patients with cellular immune defects. The major virulence factor is the polysaccharide capsule. We took advantage of a relevant murine model of disseminated meningoencephalitis to study the early events associated with blood-brain barrier (BBB) crossing. Mice were sacrificed at 1, 6, 24, and 48 hours post-intravenous inoculation, and classical histology, electron microscopy, and double immunofluorescence were used to study tissues and yeasts. Crossing of the BBB occurred early after inoculation, did not involve the choroid plexus but instead occurred at the level of the cortical capillaries, and caused early and severe damage to the structure of the microvessels. Seeding of the leptomeninges was not the primary event but occurred secondary to leakage of cortical pseudocysts. Organ invasion was associated with changes in cryptococcal capsule structure and cell size, which differed in terms of magnitude and kinetics, depending on both the organs involved, and potentially, on the bed structure of the local capillary. The rapid changes in capsule structure could contribute to inability of the host immune response to control cryptococcal infection in extrapulmonary spaces.
Insights
Cryptococcus neoformans rapidly crosses the blood-brain barrier (BBB) via cortical capillaries, not the choroid plexus, causing microvessel damage. Changes in the fungal capsule influence organ invasion and immune evasion in meningoencephalitis.
Area of Science:
- * Mycology and Infectious Diseases
- * Neuroscience and Neuroimmunology
Background:
- * Cryptococcus neoformans causes life-threatening meningoencephalitis, particularly in immunocompromised individuals.
- * The fungal polysaccharide capsule is a key virulence factor.
- * Understanding early dissemination events is crucial for developing effective therapies.
Purpose of the Study:
- * To investigate the early mechanisms of blood-brain barrier (BBB) penetration by Cryptococcus neoformans in a murine model.
- * To characterize the structural changes in the BBB and the yeast during dissemination.
- * To explore the role of cryptococcal capsule alterations in organ invasion and immune evasion.
Main Methods:
- * Intravenous inoculation of mice with Cryptococcus neoformans.
- * Time-course analysis (1, 6, 24, 48 hours post-inoculation) using histology, electron microscopy, and double immunofluorescence.
- * Examination of yeast and host tissue interactions within various organs.
Main Results:
- * Early BBB crossing occurred through cortical capillaries, causing significant microvessel damage.
- * Leptomeningeal seeding was a secondary event, following leakage from cortical pseudocysts.
- * Cryptococcal capsule structure and cell size changed dynamically, varying by organ and capillary bed structure.
Conclusions:
- * Cryptococcus neoformans breaches the BBB early via direct invasion of cortical capillaries.
- * Dynamic alterations in the yeast capsule are associated with organ invasion and may hinder host immune responses.
- * These findings highlight the importance of early BBB integrity and fungal capsule dynamics in cryptococcal meningoencephalitis pathogenesis.
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