An optimized in vitro blood-brain barrier model reveals bidirectional transmigration of African trypanosome strains.

2.50
Hdl Handle:
http://hdl.handle.net/10033/344210
Title:
An optimized in vitro blood-brain barrier model reveals bidirectional transmigration of African trypanosome strains.
Authors:
Untucht, Christopher; Rasch, Janine; Fuchs, Elena; Rohde, Manfred; Bergmann, Simone; Steinert, Michael
Abstract:
The transmigration of African trypanosomes across the human blood-brain barrier (BBB) is the critical step during the course of human African trypanosomiasis. The parasites Trypanosoma brucei gambiense and T. b. rhodesiense are transmitted to humans during the bite of tsetse flies. Trypanosomes multiply within the bloodstream and finally invade the central nervous system (CNS), which leads to the death of untreated patients. This project focused on the mechanisms of trypanosomal traversal across the BBB. In order to establish a suitable in vitro BBB model for parasite transmigration, different human cell lines were used, including ECV304, HBMEC and HUVEC, as well as C6 rat astrocytes. Validation of the BBB models with Escherichia coli HB101 and E. coli K1 revealed that a combination of ECV304 cells seeded on Matrigel as a semi-synthetic basement membrane and C6 astrocytes resulted in an optimal BBB model system. The BBB model showed selective permeability for the pathogenic E. coli K1 strain, and African trypanosomes were able to traverse the optimized ECV304-C6 BBB efficiently. Furthermore, coincubation indicated that paracellular macrophage transmigration does not facilitate trypanosomal BBB traversal. An inverse assembly of the BBB model demonstrated that trypanosomes were also able to transmigrate the optimized ECV304-C6 BBB backwards, indicating the relevance of the CNS as a possible reservoir of a relapsing parasitaemia.
Citation:
An optimized in vitro blood-brain barrier model reveals bidirectional transmigration of African trypanosome strains. 2011, 157 (Pt 10):2933-41 Microbiology (Reading, Engl.)
Journal:
Microbiology (Reading, England)
Issue Date:
Oct-2011
URI:
http://hdl.handle.net/10033/344210
DOI:
10.1099/mic.0.049106-0
PubMed ID:
21737496
Type:
Article
Language:
en
ISSN:
1465-2080
Appears in Collections:
Publications of Dept. Medizinische Mikrobiologie (MMIK)

Full metadata record

DC FieldValue Language
dc.contributor.authorUntucht, Christopheren
dc.contributor.authorRasch, Janineen
dc.contributor.authorFuchs, Elenaen
dc.contributor.authorRohde, Manfreden
dc.contributor.authorBergmann, Simoneen
dc.contributor.authorSteinert, Michaelen
dc.date.accessioned2015-02-05T10:02:34Z-
dc.date.available2015-02-05T10:02:34Z-
dc.date.issued2011-10-
dc.identifier.citationAn optimized in vitro blood-brain barrier model reveals bidirectional transmigration of African trypanosome strains. 2011, 157 (Pt 10):2933-41 Microbiology (Reading, Engl.)en
dc.identifier.issn1465-2080-
dc.identifier.pmid21737496-
dc.identifier.doi10.1099/mic.0.049106-0-
dc.identifier.urihttp://hdl.handle.net/10033/344210-
dc.description.abstractThe transmigration of African trypanosomes across the human blood-brain barrier (BBB) is the critical step during the course of human African trypanosomiasis. The parasites Trypanosoma brucei gambiense and T. b. rhodesiense are transmitted to humans during the bite of tsetse flies. Trypanosomes multiply within the bloodstream and finally invade the central nervous system (CNS), which leads to the death of untreated patients. This project focused on the mechanisms of trypanosomal traversal across the BBB. In order to establish a suitable in vitro BBB model for parasite transmigration, different human cell lines were used, including ECV304, HBMEC and HUVEC, as well as C6 rat astrocytes. Validation of the BBB models with Escherichia coli HB101 and E. coli K1 revealed that a combination of ECV304 cells seeded on Matrigel as a semi-synthetic basement membrane and C6 astrocytes resulted in an optimal BBB model system. The BBB model showed selective permeability for the pathogenic E. coli K1 strain, and African trypanosomes were able to traverse the optimized ECV304-C6 BBB efficiently. Furthermore, coincubation indicated that paracellular macrophage transmigration does not facilitate trypanosomal BBB traversal. An inverse assembly of the BBB model demonstrated that trypanosomes were also able to transmigrate the optimized ECV304-C6 BBB backwards, indicating the relevance of the CNS as a possible reservoir of a relapsing parasitaemia.en
dc.language.isoenen
dc.subject.meshAnimalsen
dc.subject.meshBlood-Brain Barrieren
dc.subject.meshCell Lineen
dc.subject.meshHumansen
dc.subject.meshMiceen
dc.subject.meshModels, Biologicalen
dc.subject.meshRatsen
dc.subject.meshTrypanosoma brucei gambienseen
dc.subject.meshTrypanosoma brucei rhodesienseen
dc.subject.meshTrypanosomiasis, Africanen
dc.titleAn optimized in vitro blood-brain barrier model reveals bidirectional transmigration of African trypanosome strains.en
dc.typeArticleen
dc.identifier.journalMicrobiology (Reading, England)en

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