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Review
. 2023 Dec 11:13:1331429.
doi: 10.3389/fcimb.2023.1331429. eCollection 2023.

Macropinocytosis as a potential mechanism driving neurotropism of Cryptococcus neoformans

Dylan M Lanser #  1 , Amelia B Bennett #  1 , Kiem Vu #  1 , Angie Gelli  1
Affiliations
Review

Macropinocytosis as a potential mechanism driving neurotropism of Cryptococcus neoformans

Dylan M Lanser et al. Front Cell Infect Microbiol. .

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.

Keywords: CD44; EphA2; Ephrin receptor; EphrinA1; blood-brain barrier; brain endothelial cells; macropinocytosis; transcytosis.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

Figures

Figure 1
Figure 1
Adherence and internalization of C. neoformans depends on the (1) hyaluronic acid receptor (CD44) and an ephrin receptor tyrosine kinase (EphA2) - triggering membrane and cytoskeleton remodeling (2). EphA2-mediated signaling promotes macropinocytic transcytosis and opens a paracellular path via the re-modeling of tight junctions (3), thus facilitating invasion of the central nervous system by C. neoformans (4). Created with Biorender.com.
See this image and copyright information in PMC

References

    1. Aaron P. A., Jamklang M., Uhrig J. P., Gelli A. (2018). The blood-brain barrier internalises Cryptococcus neoformans via the EphA2-tyrosine kinase receptor. Cell Microbiol. 20 (3), 138–149. doi: 10.1111/cmi.12811 - DOI - PMC - PubMed
    1. Ajikumar A., Long M. B., Heath P. R., Wharton S. B., Ince P. G., Ridger V. C., et al. . (2019). Neutrophil-derived microvesicle induced dysfunction of brain microvascular endothelial cells in vitro . Int. J. Mol. Sci. 20 (20). doi: 10.3390/ijms20205227 - DOI - PMC - PubMed
    1. Bandyopadhyay C., Valiya-Veettil M., Dutta D., Chakraborty S., Chandran B. (2014). CIB1 synergizes with EphrinA2 to regulate Kaposi’s sarcoma-associated herpesvirus macropinocytic entry in human microvascular dermal endothelial cells. PloS Pathog. 10 (2), e1003941. doi: 10.1371/journal.ppat.1003941 - DOI - PMC - PubMed
    1. Bauherr S., Larsberg F., Petrich A., Sperber H. S., Klose-Grzelka V., Luckner M., et al. . (2020). Macropinocytosis and clathrin-dependent endocytosis play pivotal roles for the infectious entry of puumala virus. J. Virol. 94 (14). doi: 10.1128/JVI.00184-20 - DOI - PMC - PubMed
    1. Bloomfield G., Kay R. R. (2016). Uses and abuses of macropinocytosis. J. Cell Sci. 129 (14), 2697–2705. doi: 10.1242/jcs.176149 - DOI - PubMed

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