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Visualizing Non-lytic Exocytosis of Cryptococcus neoformans from Macrophages Using Digital Light Microscopy
Published on: October 21, 2014
Pathogenesis of cerebral Cryptococcus neoformans infection after fungemia
Fabrice Chrétien1, Olivier Lortholary, Imad Kansau
1Laboratoire de Neuropathologie, Faculté de Médecine Paris-Ouest, Hôpital Raymond-Poincaré, Garches, Paris, France. chretien.fabrice@aol.com
Abstract:
The pathogenesis of cerebral infection after Cryptococcus neoformans fungemia in outbred mice was investigated. Confocal microscopy and cultures on ficoll-hypaque gradient-separated blood cells were used to detect yeasts in the cytoplasms of monocytes. In semithin brain sections, poorly capsulated yeasts were seen in macrophages in the leptomeningeal space, in monocytes circulating in leptomeningeal capillaries, or in the endothelial cells themselves, strengthening the hypothesis that monocytes and endothelial cells play key roles in the pathogenesis of cryptococcal meningitis. Similar fungal loads and cellular reactions were seen in mice and in 1 patient with acquired immune deficiency syndrome (AIDS), all with acute cryptococcal meningoencephalitis, and in mice and in 1 patient with AIDS, all with cured cryptococcal infection. Immunostaining revealed both the presence of cryptococcal polysaccharide in various brain cells and antigenic variability both from yeast cell to yeast cell and over time. Thus, our data established the relevance and interest that this experimental model has for investigation of the pathogenesis of human cryptococcal meningitis.
Insights
This study reveals how Cryptococcus neoformans causes brain infections, highlighting the roles of monocytes and endothelial cells in cryptococcal meningitis pathogenesis. The findings in mice and AIDS patients offer insights into fungal brain invasion and immune responses.
Area of Science:
- Infectious Diseases
- Neuroscience
- Immunology
Background:
- Cryptococcus neoformans fungemia can lead to serious cerebral infections, particularly cryptococcal meningitis.
- Understanding the early pathogenesis of fungal invasion into the central nervous system is crucial for developing effective treatments.
Observation:
- Yeasts were detected within monocytes and endothelial cells in brain tissues of infected mice.
- Macrophages in the leptomeningeal space also harbored yeasts, suggesting multiple routes of fungal entry and spread.
- Similar cellular interactions and fungal loads were observed in a murine model and a patient with acquired immune deficiency syndrome (AIDS).
Findings:
- Monocytes and endothelial cells are implicated as key players in the pathogenesis of cryptococcal meningitis.
- The experimental model demonstrated the presence of cryptococcal polysaccharide in brain cells and significant antigenic variability.
- The study established the relevance of the murine model for investigating human cryptococcal meningitis.
Implications:
- This research provides a valuable experimental model for studying cryptococcal meningitis pathogenesis.
- Findings may inform the development of targeted therapies aimed at preventing or treating fungal brain infections.
- Understanding the cellular mechanisms of fungal invasion can aid in managing infections in immunocompromised individuals, including those with AIDS.
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