AUTHOR=Lanser Dylan M. , Bennett Amelia B. , Vu Kiem , Gelli Angie 

TITLE=Macropinocytosis as a potential mechanism driving neurotropism of Cryptococcus neoformans

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=13

YEAR=2023

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2023.1331429

DOI=10.3389/fcimb.2023.1331429

ISSN=2235-2988

ABSTRACT=<p><italic>Cryptococcus neoformans</italic> 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 <italic>C. neoformans</italic> and brain endothelial cells forms the basis for invasion and transmigration across the brain endothelium. Adherence and internalization of <italic>C. neoformans</italic> 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 <italic>C. neoformans</italic> and highlight experimental evidence supporting macropinocytosis as a potential mechanism of internalization and transcytosis. How macropinocytosis might be conclusively demonstrated in the context of <italic>C. neoformans</italic> is also discussed.</p>