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Updated: Jul 7, 2025
Macrophage Cholesterol Depletion and Its Effect on the Phagocytosis of Cryptococcus neoformans
Published on: December 19, 2014
Macropinocytosis as a potential mechanism driving neurotropism of Cryptococcus neoformans
Dylan M Lanser1, Amelia B Bennett1, Kiem Vu1
1Department of Pharmacology, School of Medicine, University of California, Davis, Davis, CA, United States.
Abstract:
Cryptococcus neoformans can invade the central nervous system by crossing the blood-brain barrier via a transcellular mechanism that relies on multiple host factors. In this narrative, we review the evidence that a direct interplay between C. neoformans and brain endothelial cells forms the basis for invasion and transmigration across the brain endothelium. Adherence and internalization of C. neoformans is dependent on transmembrane proteins, including a hyaluronic acid receptor and an ephrin receptor tyrosine kinase. We consider the role of EphA2 in facilitating the invasion of the central nervous system by C. neoformans and highlight experimental evidence supporting macropinocytosis as a potential mechanism of internalization and transcytosis. How macropinocytosis might be conclusively demonstrated in the context of C. neoformans is also discussed.
Insights
Cryptococcus neoformans invades the central nervous system by crossing the blood-brain barrier. This review details how fungal interactions with brain endothelial cells, particularly EphA2 receptor tyrosine kinase, facilitate this invasion.
Area of Science:
- Neuroscience
- Infectious Diseases
- Cell Biology
Background:
- Cryptococcus neoformans is a fungal pathogen that can cause life-threatening meningoencephalitis.
- Breaching the blood-brain barrier (BBB) is a critical step for C. neoformans to establish central nervous system (CNS) infection.
- Understanding the molecular mechanisms of C. neoformans CNS invasion is crucial for developing targeted therapies.
Purpose of the Study:
- To review the current evidence on the mechanisms by which C. neoformans invades the CNS.
- To elucidate the role of host factors, particularly brain endothelial cells and specific receptors, in fungal transmigration.
- To discuss the potential involvement of macropinocytosis in C. neoformans CNS entry.
Main Methods:
- Review of existing literature and experimental evidence.
- Analysis of studies investigating fungal adherence to and invasion of brain endothelial cells.
- Examination of the role of specific host cell receptors, including EphA2.
- Discussion of cellular uptake mechanisms like macropinocytosis.
Main Results:
- C. neoformans invasion of the CNS is mediated by a transcellular mechanism across the BBB.
- Direct interactions between C. neoformans and brain endothelial cells are essential for invasion.
- Transmembrane proteins, such as hyaluronic acid receptors and the ephrin receptor tyrosine kinase EphA2, play a significant role in fungal adherence and internalization.
- Experimental evidence suggests macropinocytosis as a potential pathway for C. neoformans internalization and transcytosis.
Conclusions:
- The interplay between C. neoformans and brain endothelial cells, involving specific host receptors like EphA2, is fundamental to CNS invasion.
- Macropinocytosis is a plausible mechanism for C. neoformans entry and transport across the BBB, warranting further investigation.
- Further research is needed to definitively demonstrate and characterize the role of macropinocytosis in C. neoformans CNS pathogenesis.
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