66
Views
0
CrossRef citations to date
0
Altmetric
Mini Review

Traversal of human and animal trypanosomes across the blood-brain barrier

&
Pages 344-351 | Received 01 Apr 2008, Published online: 10 Jul 2009
 

Abstract

The neurological complications of human African trypanosomiasis (HAT) in man caused by the unicellular protozoan parasites Trypanosoma brucei gambiense and T. b. rhodesiense are a consequence of the penetration of the blood-brain barrier (BBB) by trypanosomes that enter the central nervous system (CNS). Yet the mechanisms by which African trypanosomes cross the true BBB comprised of brain microvascular endothelial cells (BMECs) remain unclear. Human BBB models used to determine how African trypanosomes initially interact in vitro with the human BBB proper suggest that parasites cross the human BBB in part by generating Ca2+ activation signals in human BMECs through the activity of parasite cysteine proteases. In vivo murine models of HAT have suggested additional mechanisms of BBB traversal by trypanosomes, with recent compelling evidence for the important role of interferon-γ in facilitating this process. A clear understanding of how trypanosomes enter the CNS is critical for both understanding the neuropathogenesis of HAT and in developing more effective drug therapies for late-stage disease.

Acknowledgements

This work was supported by NIH grant R01 AI1464-01 (D. J. Grab). The authors would also like to thank Dr. Avindra Nath (Johns Hopkins University) for critical reading of the original manuscript, and the laboratory work of Dr. Olga V. Nikolskaia is also acknowledged. D. J. Grab dedicates this work to the families of David Drummond and Mike Amos, two friends whose hearts never left their beloved Kenya. Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.