ArticleCellular microbiology2018
The blood-brain barrier internalises Cryptococcus neoformans via the EphA2-tyrosine kinase receptor.
Article in Cellular microbiology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 69 citations in OpenAlex.
- Cross-expression meta-analysis of mouse brain slices reveals coordinated gene expression across spatially adjacent cells.Genome biology · 2025Pooled it
- Immune Modulation and Evasion byACS omega · 2026Review
- Cryptococcal Infection Across Disease Stages: Host-Pathogen Interactions, Tissue Niches, and Translational Priorities.Pathogens (Basel, Switzerland) · 2026Review
- The Pain Is in the Brain With the Sugar-Coated Killer.The Journal of infectious diseases · 2025Review
- Dcaf15-mediated EphA2 degradation triggers disruption of the blood-brain barrier during Streptococcus suis meningitis.Communications biology · 2025Article
- Macropinocytosis mediates neurotropism ofResearch square · 2025Article
- Cross-expression meta-analysis of 695 brain samples reveals coordinated gene expression across spatially adjacent cells.bioRxiv : the preprint server for biology · 2025Article
- Mechanisms and Virulence Factors ofJournal of fungi (Basel, Switzerland) · 2024Review
- Preclinical Models for Cryptococcosis of the CNS and Their Characterization Using In Vivo Imaging Techniques.Journal of fungi (Basel, Switzerland) · 2024Review
- BIOMOLECULAR ACTIVITY OF CRYPTOCOCCUS DURING CRYPTOCOCCOSIS: A REVIEW OF MOLECULAR INTERACTIONS OF CRYPTOCOCCUS WITH HUMAN IMMUNE SYSTEM AND BLOOD-BRAIN-BARRIER.African journal of infectious diseases · 2024Article
- The pathways and the mechanisms by whichMycology · 2024Review
- Eph receptors and ephrins in cancer progression.Nature reviews. Cancer · 2024Review
- A multi-arm, parallel, preclinical study investigating the potential benefits of acetazolamide, candesartan, and triciribine in combination with fluconazole for the treatment of cryptococcal meningoencephalitis.European journal of pharmacology · 2023Article
- Macropinocytosis as a potential mechanism driving neurotropism ofFrontiers in cellular and infection microbiology · 2023Review
- Review
- Targeting Host Tyrosine Kinase Receptor EPHA2 Signaling Affects Uropathogen Infection in Human Bladder Epithelial Cells.Pathogens (Basel, Switzerland) · 2022Article
- IL-23 signaling prevents ferroptosis-driven renal immunopathology during candidiasis.Nature communications · 2022Article
- Elevated Intracranial Pressure in Cryptococcal Meningoencephalitis: Examining Old, New, and Promising Drug Therapies.Pathogens (Basel, Switzerland) · 2022Review
- Identification of lncRNAs and Their Regulatory Relationships with mRNAs in Response toBioMed research international · 2022Article
- Fungal CNS Infections in Africa: The Neuroimmunology of Cryptococcal Meningitis.Frontiers in immunology · 2022Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Cryptococcus neoformans is an opportunistic fungal pathogen that causes life-threatening meningitis most commonly in populations with impaired immunity. Here, we resolved the transcriptome of the human brain endothelium challenged with C. neoformans to establish whether C. neoformans invades the CNS by co-opting particular signalling pathways as a means to promote its own entry. Among the 5 major pathways targeted by C. neoformans, the EPH-EphrinA1 (EphA2) tyrosine kinase receptor-signalling pathway was examined further. Silencing the EphA2 receptor transcript in a human brain endothelial cell line or blocking EphA2 activity with an antibody or chemical inhibitor prevented transmigration of C. neoformans in an in vitro model of the blood-brain barrier (BBB). In contrast, treating brain endothelial cells with an EphA2 chemical agonist or an EphA2 ligand promoted greater migration of fungal cells across the BBB. C. neoformans activated the EPH-tyrosine kinase pathway through a CD44-dependent phosphorylation of EphA2, promoting clustering and internalisation of EphA2 receptors. Moreover, HEK293T cells expressing EphA2 revealed an association between EphA2 and C. neoformans that boosted internalisation of C. neoformans. Collectively, the results suggest that C. neoformans promotes EphA2 activity via CD44, and this in turn creates a permeable barrier that facilitates the migration of C. neoformans across the BBB.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.