Cryptococcal transmigration across a model brain blood-barrier: Evidence of the Trojan horse mechanism and differences between Cryptococcus neoformans var. grubii strain H99 and Cryptococcus gattii strain R265

Sorrell, TC; Juillard, PG; Djordjevic, JT; Kaufman-Francis, K; Dietmann, A; Milonig, A; Combes, V; Grau, GER

Cryptococcal transmigration across a model brain blood-barrier: Evidence of the Trojan horse mechanism and differences between Cryptococcus neoformans var. grubii strain H99 and Cryptococcus gattii strain R265

Sorrell, TC Juillard, PG Djordjevic, JT Kaufman-Francis, K Dietmann, A Milonig, A Combes, V

Grau, GER

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Publication Type:: Journal Article
Citation:: Microbes and Infection, 2016, 18 (1), pp. 57 - 67
Issue Date:: 2016-01-01

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Field	Value	Language
dc.contributor.author	Sorrell, TC	en_US
dc.contributor.author	Juillard, PG	en_US
dc.contributor.author	Djordjevic, JT	en_US
dc.contributor.author	Kaufman-Francis, K	en_US
dc.contributor.author	Dietmann, A	en_US
dc.contributor.author	Milonig, A	en_US
dc.contributor.author	Combes, V https://orcid.org/0000-0003-2178-3596	en_US
dc.contributor.author	Grau, GER	en_US
dc.date.available	2020-05-25T19:09:09Z
dc.date.issued	2016-01-01	en_US
dc.identifier.citation	Microbes and Infection, 2016, 18 (1), pp. 57 - 67	en_US
dc.identifier.issn	1286-4579	en_US
dc.identifier.uri	http://hdl.handle.net/10453/40906
dc.description.abstract	© 2015 Institut Pasteur. Cryptococcus neoformans (. Cn) and Cryptococcus gattii (Cg) cause neurological disease and cross the BBB as free cells or in mononuclear phagocytes via the Trojan horse mechanism, although evidence for the latter is indirect. There is emerging evidence that Cn and the North American outbreak Cg strain (R265) more commonly cause neurological and lung disease, respectively. We have employed a widely validated in vitro model of the BBB, which utilizes the hCMEC/D3 cell line derived from human brain endothelial cells (HBEC) and the human macrophage-like cell line, THP-1, to investigate whether transport of dual fluorescence-labelled Cn and Cg across the BBB occurs within macrophages. We showed that phagocytosis of Cn by non-interferon (IFN)-γ stimulated THP-1 cells was higher than that of Cg. Although Cn and Cg-loaded THP-1 bound similarly to TNF-activated HBECs under shear stress, more Cn-loaded macrophages were transported across an intact HBEC monolayer, consistent with the predilection of Cn for CNS infection. Furthermore, Cn exhibited a higher rate of expulsion from transmigrated THP-1 compared with Cg. Our results therefore provide further evidence for transmigration of both Cn and Cg via the Trojan horse mechanism and a potential explanation for the predilection of Cn to cause CNS infection.	en_US
dc.relation.ispartof	Microbes and Infection	en_US
dc.relation.isbasedon	10.1016/j.micinf.2015.08.017	en_US
dc.subject.classification	Microbiology	en_US
dc.subject.mesh	Blood-Brain Barrier	en_US
dc.subject.mesh	Cells, Cultured	en_US
dc.subject.mesh	Macrophages	en_US
dc.subject.mesh	Endothelial Cells	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Cryptococcus neoformans	en_US
dc.subject.mesh	Cell Movement	en_US
dc.subject.mesh	Models, Biological	en_US
dc.subject.mesh	Cryptococcus gattii	en_US
dc.title	Cryptococcal transmigration across a model brain blood-barrier: Evidence of the Trojan horse mechanism and differences between Cryptococcus neoformans var. grubii strain H99 and Cryptococcus gattii strain R265	en_US
dc.type	Journal Article
utslib.citation.volume	1	en_US
utslib.citation.volume	18	en_US
utslib.for	0605 Microbiology	en_US
utslib.for	1108 Medical Microbiology	en_US
utslib.for	1107 Immunology	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
utslib.copyright.status	open_access
pubs.issue	1	en_US
pubs.publication-status	Published	en_US
pubs.volume	18	en_US

Abstract:

© 2015 Institut Pasteur. Cryptococcus neoformans (. Cn) and Cryptococcus gattii (Cg) cause neurological disease and cross the BBB as free cells or in mononuclear phagocytes via the Trojan horse mechanism, although evidence for the latter is indirect. There is emerging evidence that Cn and the North American outbreak Cg strain (R265) more commonly cause neurological and lung disease, respectively. We have employed a widely validated in vitro model of the BBB, which utilizes the hCMEC/D3 cell line derived from human brain endothelial cells (HBEC) and the human macrophage-like cell line, THP-1, to investigate whether transport of dual fluorescence-labelled Cn and Cg across the BBB occurs within macrophages. We showed that phagocytosis of Cn by non-interferon (IFN)-γ stimulated THP-1 cells was higher than that of Cg. Although Cn and Cg-loaded THP-1 bound similarly to TNF-activated HBECs under shear stress, more Cn-loaded macrophages were transported across an intact HBEC monolayer, consistent with the predilection of Cn for CNS infection. Furthermore, Cn exhibited a higher rate of expulsion from transmigrated THP-1 compared with Cg. Our results therefore provide further evidence for transmigration of both Cn and Cg via the Trojan horse mechanism and a potential explanation for the predilection of Cn to cause CNS infection.

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http://hdl.handle.net/10453/40906