Generation of neuroinflammation in human African trypanosomiasis

Rodgers, J. , Steiner, I. and Kennedy, P. G.E. (2019) Generation of neuroinflammation in human African trypanosomiasis. Neurology: Neuroimmunology and Neuroinflammation, 6(6), e610. (doi: 10.1212/NXI.0000000000000610) (PMID:31467039) (PMCID:PMC6745723)

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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.

Item Type:Articles
Additional Information:Funded by University of Glasgow.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Rodgers, Dr Jean and Kennedy, Professor Peter
Authors: Rodgers, J., Steiner, I., and Kennedy, P. G.E.
College/School:College of Medical Veterinary and Life Sciences > Institute of Biodiversity Animal Health and Comparative Medicine
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Neurology: Neuroimmunology and Neuroinflammation
Publisher:Wolters Kluwer Health/LWW
ISSN:2332-7812
ISSN (Online):2332-7812
Published Online:29 August 2019
Copyright Holders:Copyright © 2019 The Authors
First Published:First published in Neurology: Neuroimmunology and Neuroinflammation 6(6):e610
Publisher Policy:Reproduced under a Creative Commons License

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