Intravital imaging of a massive lymphocyte response in the cortical dura of mice after peripheral infection by trypanosomes

Coles, J. A., Myburgh, E. , Ritchie, R., Hamilton, A., Rodgers, J. , Mottram, J. C. , Barrett, M. P. and Brewer, J. M. (2015) Intravital imaging of a massive lymphocyte response in the cortical dura of mice after peripheral infection by trypanosomes. PLoS Neglected Tropical Diseases, 9(4), e0003714. (doi: 10.1371/journal.pntd.0003714) (PMID:25881126) (PMCID:PMC4400075)

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Peripheral infection by Trypanosoma brucei, the protozoan responsible for sleeping sickness, activates lymphocytes, and, at later stages, causes meningoencephalitis. We have videoed the cortical meninges and superficial parenchyma of C56BL/6 reporter mice infected with T.b.brucei. By use of a two-photon microscope to image through the thinned skull, the integrity of the tissues was maintained. We observed a 47-fold increase in CD2+ T cells in the meninges by 12 days post infection (dpi). CD11c+ dendritic cells also increased, and extravascular trypanosomes, made visible either by expression of a fluorescent protein, or by intravenous injection of furamidine, appeared. The likelihood that invasion will spread from the meninges to the parenchyma will depend strongly on whether the trypanosomes are below the arachnoid membrane, or above it, in the dura. Making use of optical signals from the skull bone, blood vessels and dural cells, we conclude that up to 40 dpi, the extravascular trypanosomes were essentially confined to the dura, as were the great majority of the T cells. Inhibition of T cell activation by intraperitoneal injection of abatacept reduced the numbers of meningeal T cells at 12 dpi and their mean speed fell from 11.64 ± 0.34 μm/min (mean ± SEM) to 5.2 ± 1.2 μm/min (p = 0.007). The T cells occasionally made contact lasting tens of minutes with dendritic cells, indicative of antigen presentation. The population and motility of the trypanosomes tended to decline after about 30 dpi. We suggest that the lymphocyte infiltration of the meninges may later contribute to encephalitis, but have no evidence that the dural trypanosomes invade the parenchyma.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Brewer, Professor James and Coles, Dr Jonathan and Ritchie, Mr Ryan and Myburgh, Dr Elmarie and Barrett, Professor Michael and Hamilton, Mrs Alana and Mottram, Professor Jeremy and Rodgers, Dr Jean
Authors: Coles, J. A., Myburgh, E., Ritchie, R., Hamilton, A., Rodgers, J., Mottram, J. C., Barrett, M. P., and Brewer, J. M.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine
Journal Name:PLoS Neglected Tropical Diseases
Publisher:Public Library of Science
ISSN (Online):1935-2735
Copyright Holders:Copyright © 2015 The Authors
First Published:First published in PLOS Neglected Tropical Diseases 9(4):e0003714
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
522031In vivo imaging models of African trypanosomiasis to support drug discovery programmes.Michael BarrettGates Foundation (GATES)OPPGH5337III - PARASITOLOGY
371798The Wellcome Centre for Molecular Parasitology ( Core Support )Andrew WatersWellcome Trust (WELLCOME)085349/B/08/ZIII - PARASITOLOGY