Trypanosoma brucei brucei invasion and T-cell infiltration of the brain parenchyma in experimental sleeping sickness: timing and correlation with functional changes

Laperchia, C., Palomba, M., Etet, P. F. S., Rodgers, J. , Bradley, B., Montague, P., Grassi-Zucconi, G., Kennedy, P. G.E. and Bentivoglio, M. (2016) Trypanosoma brucei brucei invasion and T-cell infiltration of the brain parenchyma in experimental sleeping sickness: timing and correlation with functional changes. PLoS Neglected Tropical Diseases, 10(12), e0005242. (doi:10.1371/journal.pntd.0005242) (PMID:28002454) (PMCID:PMC5217973)

[img]
Preview
Text
132541.pdf - Published Version
Available under License Creative Commons Attribution.

2MB

Abstract

Background: The timing of Trypanosoma brucei entry into the brain parenchyma to initiate the second, meningoencephalitic stage of human African trypanosomiasis or sleeping sickness is currently debated and even parasite invasion of the neuropil has been recently questioned. Furthermore, the relationship between neurological features and disease stage are unclear, despite the important diagnostic and therapeutic implications. Methodology: Using a rat model of chronic Trypanosoma brucei brucei infection we determined the timing of parasite and T-cell neuropil infiltration and its correlation with functional changes. Parasite DNA was detected using trypanosome-specific PCR. Body weight and sleep structure alterations represented by sleep-onset rapid eye movement (SOREM) periods, reported in human and experimental African trypanosomiasis, were monitored. The presence of parasites, as well as CD4+ and CD8+ T-cells in the neuropil was assessed over time in the brain of the same animals by immunocytochemistry and quantitative analyses. Principal findings: Trypanosome DNA was present in the brain at day 6 post-infection and increased more than 15-fold by day 21. Parasites and T-cells were observed in the parenchyma from day 9 onwards. Parasites traversing blood vessel walls were observed in the hypothalamus and other brain regions. Body weight gain was reduced from day 7 onwards. SOREM episodes started in most cases early after infection, with an increase in number and duration after parasite neuroinvasion. Conclusion: These findings demonstrate invasion of the neuropil over time, after an initial interval, by parasites and lymphocytes crossing the blood-brain barrier, and show that neurological features can precede this event. The data thus challenge the current clinical and cerebrospinal fluid criteria of disease staging.

Item Type:Articles
Additional Information:Other funding from WT089992MA
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Montague, Dr Paul and Kennedy, Professor Peter and Bradley, Mrs Barbara and Rodgers, Dr Jean
Authors: Laperchia, C., Palomba, M., Etet, P. F. S., Rodgers, J., Bradley, B., Montague, P., Grassi-Zucconi, G., Kennedy, P. G.E., and Bentivoglio, M.
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:PLoS Neglected Tropical Diseases
Publisher:Public Library of Science
ISSN:1935-2727
ISSN (Online):1935-2735
Copyright Holders:Copyright © 2016 Laperchia et al.
First Published:First published in PLoS Neglected Tropical Diseases 10(12):e0005242
Publisher Policy:Reproduced under a Creative Commons License

University Staff: Request a correction | Enlighten Editors: Update this record

Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
554901Defining the role of kynurenine pathway metabolites in the inflammatory response to trypanosome invasion of the CNSPeter KennedyWellcome Trust (WELLCOME)094691/Z/10/ZIII - PARASITOLOGY