Central nervous system parasitosis and neuroinflammation ameliorated by systemic IL-10 administration in trypanosoma brucei-Infected mice

Rodgers, J. , Bradley, B., Kennedy, P. G.E. and Sternberg, J. M. (2015) Central nervous system parasitosis and neuroinflammation ameliorated by systemic IL-10 administration in trypanosoma brucei-Infected mice. PLoS Neglected Tropical Diseases, 9(10), e0004201. (doi:10.1371/journal.pntd.0004201) (PMID:26505761) (PMCID:PMC4624684)

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Abstract

Invasion of the central nervous system (CNS) by African trypanosomes represents a critical step in the development of human African trypanosomiasis. In both clinical cases and experimental mouse infections it has been demonstrated that predisposition to CNS invasion is associated with a type 1 systemic inflammatory response. Using the Trypanosoma brucei brucei GVR35 experimental infection model, we demonstrate that systemic delivery of the counter-inflammatory cytokine IL-10 lowers plasma IFN-γ and TNF-α concentrations, CNS parasitosis and ameliorates neuro-inflammatory pathology and clinical symptoms of disease. The results provide evidence that CNS invasion may be susceptible to immunological attenuation.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Kennedy, Professor Peter and Bradley, Mrs Barbara and Rodgers, Dr Jean
Authors: Rodgers, J., Bradley, B., Kennedy, P. G.E., and Sternberg, J. 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:1935-2735
ISSN (Online):1935-2735
Copyright Holders:Copyright © 2015 Rodgers et al.
First Published:First published in PLoS Neglected Tropical Diseases 9(10)e0004201
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
457901Defining the therapeutic role of IL-10 in African trypanosomiasis.Peter KennedyWellcome Trust (WELLCOME)082786/Z/07/ZIII - PARASITOLOGY
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