Generation of neuroinflammation in human African trypanosomiasis
Citation Manager Formats
Make Comment
See Comments

Abstract
Human African trypanosomiasis (HAT) is caused by infection due to protozoan parasites of the Trypanosoma genus and is a major fatal disease throughout sub-Saharan Africa. After an early hemolymphatic stage in which the peripheral tissues are infected, the parasites enter the CNS causing a constellation of neurologic features. Although the CNS stage of HAT has been recognized for over a century, the mechanisms generating the neuroinflammatory response are complex and not well understood. Therefore a better understanding of the mechanisms utilized by the parasites to gain access to the CNS compartment is critical to explaining the generation of neuroinflammation. Contrast-enhanced MRI in a murine model of HAT has shown an early and progressive deterioration of blood-CNS barrier function after trypanosome infection that can be reversed following curative treatment. However, further studies are required to clarify the molecules involved in this process. Another important determinant of brain inflammation is the delicate balance of proinflammatory and counterinflammatory mediators. In mouse models of HAT, proinflammatory mediators such as tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and CXCL10 have been shown to be crucial to parasite CNS invasion while administration of interleukin (IL)-10, a counter inflammatory molecule, reduces the CNS parasite burden as well as the severity of the neuroinflammatory response and the clinical symptoms associated with the infection. This review focuses on information, gained from both infected human samples and animal models of HAT, with an emphasis on parasite CNS invasion and the development of neuroinflammation.
Glossary
- BBB=
- blood-brain barrier;
- BCSFB=
- blood-CSF barrier;
- HAT=
- human African trypanosomiasis;
- HBMEC=
- human brain microvascular endothelial cell;
- MMP=
- matrix metalloproteinases;
- PTRE=
- post-treatment reactive encephalopathy;
- TEER=
- transendothelial electrical resistance;
- TLR=
- Toll-like receptor;
- WBC=
- white blood cell
Footnotes
Go to Neurology.org/NN for full disclosures. Funding information are provided at the end of the article.
The Article Processing Charge was funded by Neurology: Neuroimmunology & Neuroinflammation.
- Received April 15, 2019.
- Accepted in final form July 29, 2019.
- Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
Letters: Rapid online correspondence
REQUIREMENTS
You must ensure that your Disclosures have been updated within the previous six months. Please go to our Submission Site to add or update your Disclosure information.
Your co-authors must send a completed Publishing Agreement Form to Neurology Staff (not necessary for the lead/corresponding author as the form below will suffice) before you upload your comment.
If you are responding to a comment that was written about an article you originally authored:
You (and co-authors) do not need to fill out forms or check disclosures as author forms are still valid
and apply to letter.
Submission specifications:
- Submissions must be < 200 words with < 5 references. Reference 1 must be the article on which you are commenting.
- Submissions should not have more than 5 authors. (Exception: original author replies can include all original authors of the article)
- Submit only on articles published within 6 months of issue date.
- Do not be redundant. Read any comments already posted on the article prior to submission.
- Submitted comments are subject to editing and editor review prior to posting.
You May Also be Interested in
Hastening the Diagnosis of Amyotrophic Lateral Sclerosis
Dr. Brian Callaghan and Dr. Kellen Quigg
► Watch
Related Articles
- No related articles found.
Alert Me
Recommended articles
-
Clinical Implications of Neuroscience Research
Extracellular matrix in the CNSDynamic structure and clinical correlationsEduardo E. Benarroch et al.Neurology, September 23, 2015 -
Articles
Expression of matrix metalloproteinases in the muscle of patients with inflammatory myopathiesYoung-Chul Choi, Marinos C. Dalakas et al.Neurology, January 11, 2000 -
Articles
Laminin α2 chain-deficient congenital muscular dystrophyVariable epitope expression in severe and mild casesR. D. Cohn, R. Herrmann, L. Sorokin et al.Neurology, July 01, 1998 -
Clinical Implications of Neuroscience Research
Choroid plexus–CSF systemRecent developments and clinical correlationsEduardo E. Benarroch et al.Neurology, December 18, 2015