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

Yun C. Chang, Monique Stins, Michael J. McCaffery, Georgina F. Miller, Dan R. Pare, Tapen Dam, Maneesh Paul-Satyasee, Kwang Sik Kim, Kyung J. Kwon-Chung

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)4985-4995
Number of pages11
JournalInfection and Immunity
Volume72
Issue number9
DOIs
StatePublished - Sep 2004

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Cryptococcus neoformans
Blood-Brain Barrier
Central Nervous System
Yeasts
Brain
Endothelial Cells
Transcytosis
Cryptococcosis
Meningoencephalitis
Choroid Plexus
Neuropil
Microvilli
Intravenous Injections
Endothelium
Observation
Lung
Membranes

ASJC Scopus subject areas

  • Immunology

Cite this

Cryptococcal yeast cells invade the central nervous system via transcellular penetration of the blood-brain barrier. / Chang, Yun C.; Stins, Monique; McCaffery, Michael J.; Miller, Georgina F.; Pare, Dan R.; Dam, Tapen; Paul-Satyasee, Maneesh; Kim, Kwang Sik; Kwon-Chung, Kyung J.

In: Infection and Immunity, Vol. 72, No. 9, 09.2004, p. 4985-4995.

Research output: Contribution to journalArticle

Chang, Yun C. ; Stins, Monique ; McCaffery, Michael J. ; Miller, Georgina F. ; Pare, Dan R. ; Dam, Tapen ; Paul-Satyasee, Maneesh ; Kim, Kwang Sik ; Kwon-Chung, Kyung J. / Cryptococcal yeast cells invade the central nervous system via transcellular penetration of the blood-brain barrier. In: Infection and Immunity. 2004 ; Vol. 72, No. 9. pp. 4985-4995.
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