Cryptococcal yeast cells invade the central nervous system via transcellular penetration of the blood-brain barrier.

Abstract:

:Cryptococcal meningoencephalitis develops as a result of hematogenous dissemination of inhaled Cryptococcus neoformans from the lung to the brain. The mechanism(s) by which C. neoformans crosses the blood-brain barrier (BBB) is a key unresolved issue in cryptococcosis. We used both an in vivo mouse model and an in vitro model of the human BBB to investigate the cryptococcal association with and traversal of the BBB. Exposure of human brain microvascular endothelial cells (HBMEC) to C. neoformans triggered the formation of microvillus-like membrane protrusions within 15 to 30 min. Yeast cells of C. neoformans adhered to and were internalized by the HBMEC, and they crossed the HBMEC monolayers via a transcellular pathway without affecting the monolayer integrity. The histopathology of mouse brains obtained after intravenous injection of C. neoformans showed that the yeast cells either were associated with endothelial cells or escaped from the brain capillary vessels into the neuropil by 3 h. C. neoformans was found in the brain parenchyma away from the vessels by 22 h. Association of C. neoformans with the choroid plexus, however, was not detected during up to 10 days of observation. Our findings indicate that C. neoformans cells invade the central nervous system by transcellular crossing of the endothelium of the BBB.

journal_name

Infect Immun

journal_title

Infection and immunity

authors

Chang YC,Stins MF,McCaffery MJ,Miller GF,Pare DR,Dam T,Paul-Satyaseela M,Kim KS,Kwon-Chung KJ

doi

10.1128/IAI.72.9.4985-4995.2004

keywords:

subject

Has Abstract

pub_date

2004-09-01 00:00:00

pages

4985-95

issue

9

eissn

0019-9567

issn

1098-5522

pii

72/9/4985

journal_volume

72

pub_type

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