Macropinocytosis mediates neurotropism of Cryptococcus neoformans in a human organoid model of the blood-brain barrier
- 1Department of Pharmacology, School of Medicine, University of California, Davis, CA USA
- 2Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, OH USA
Abstract
The opportunistic and neuroinvasive fungus, Cryptococcus neoformans (Cn), causes a life-threatening brain infection that despite treatment can cause long-term cognitive deficiencies. Studies have shown that Cn can infiltrate the central nervous system (CNS) through a transcellular route across the brain endothelium, however, the molecular process that drives brain endothelial cells to internalize Cn remains poorly defined. Here we examine the molecular interactions between fungal cells and the brain endothelium by utilizing a human 3D organoid model of the blood–brain barrier (BBB). We show that Cn exploits the process of macropinocytosis as the mechanism of endocytosis into brain endothelial cells by recruiting CD44 and EphA2 as a molecular complex. We identified two predicted binding sites on EphA2, suggesting that the two structurally distinct regions may provide a molecular basis for cooperative signaling in brain endothelial cells that stimulate macropinocytosis as the mode of entry for Cn.
Related
- A novel mycovirus identified in clinical isolates of Cryptococcus neoformans
- The RNA-binding protein Psc1 functions downstream of the NDR/LATS kinase Cbk1 to modulate CO2 tolerance in Cryptococcus neoformans
- A SuperSelective primer-based real-time PCR platform for hypersensitive detection of azole resistance in Cryptococcus neoformans
- Mouse phospholipid phosphatase 6 regulates dendritic cell cholesterol, macropinocytosis, and allergen sensitization
- Cross-species multi-omics integration reveals lung alterations in acute kidney injury across mouse, pig, and human airway organoid models
BibTeX
@article{bennett2026macropinocytosis,
title = {{Macropinocytosis mediates neurotropism of Cryptococcus neoformans in a human organoid model of the blood-brain barrier}},
author = {Amelia B. Bennett and Dylan M. Lanser and Kiem Vu and Amita R. Sahoo and Matthias Buck and Angie Gelli},
journal = {Communications Biology},
year = {2026},
month = jul,
doi = {10.1038/s42003-026-10597-y},
url = {https://doi.org/10.1038/s42003-026-10597-y},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Macropinocytosis mediates neurotropism of Cryptococcus neoformans in a human organoid model of the blood-brain barrier
AU - Amelia B. Bennett
AU - Dylan M. Lanser
AU - Kiem Vu
AU - Amita R. Sahoo
AU - Matthias Buck
AU - Angie Gelli
PY - 2026
DA - 2026/07/07
JO - Communications Biology
DO - 10.1038/s42003-026-10597-y
UR - https://doi.org/10.1038/s42003-026-10597-y
AB - The opportunistic and neuroinvasive fungus, Cryptococcus neoformans (Cn), causes a life-threatening brain infection that despite treatment can cause long-term cognitive deficiencies. Studies have shown that Cn can infiltrate the central nervous system (CNS) through a transcellular route across the brain endothelium, however, the molecular process that drives brain endothelial cells to internalize Cn remains poorly defined. Here we examine the molecular interactions between fungal cells and the brain endothelium by utilizing a human 3D organoid model of the blood–brain barrier (BBB). We show that Cn exploits the process of macropinocytosis as the mechanism of endocytosis into brain endothelial cells by recruiting CD44 and EphA2 as a molecular complex. We identified two predicted binding sites on EphA2, suggesting that the two structurally distinct regions may provide a molecular basis for cooperative signaling in brain endothelial cells that stimulate macropinocytosis as the mode of entry for Cn.
SN - 2399-3642
ER -