Viral infection of the central nervous system exacerbates interleukin-10 receptor deficiency-mediated colitis in SJL mice

Uhde, A.-K., Herder, V. , Khan, M. A., Ciurkiewicz, M., Schaudien, D., Teich, R., Floess, S., Baumgärtner, W., Huehn, J. and Beineke, A. (2016) Viral infection of the central nervous system exacerbates interleukin-10 receptor deficiency-mediated colitis in SJL mice. PLoS ONE, 11(9), e0161883. (doi: 10.1371/journal.pone.0161883) (PMID:27611574) (PMCID:PMC5017624)

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Abstract

Theiler´s murine encephalomyelitis virus (TMEV)-infection is a widely used animal model for studying demyelinating disorders, including multiple sclerosis (MS). The immunosuppressive cytokine Interleukin (IL)-10 counteracts hyperactive immune responses and critically controls immune homeostasis in infectious and autoimmune disorders. In order to investigate the effect of signaling via Interleukin-10 receptor (IL-10R) in infectious neurological diseases, TMEV-infected SJL mice were treated with IL-10R blocking antibody (Ab) in the acute and chronic phase of the disease. The findings demonstrate that (i) Ab-mediated IL-10 neutralization leads to progressive colitis with a reduction in Foxp3+ regulatory T cells and increased numbers of CD8+CD44+ memory T cells as well as activated CD4+CD69+ and CD8+CD69+ T cells in uninfected mice. (ii) Concurrent acute TMEV-infection worsened enteric disease-mediated by IL-10R neutralization. Virus-triggered effects were associated with an enhanced activation of CD4+ T helper cells and CD8+ cytotoxic T lymphocytes and augmented cytokine expression. By contrast, (iii) IL-10R neutralization during chronic TMEV-infection was not associated with enhanced peripheral immunopathology but an increased CD3+ T cell influx in the spinal cord. IL-10R neutralization causes a breakdown in peripheral immune tolerance in genetically predisposed mice, which leads to immune-mediated colitis, resembling inflammatory bowel disease. Hyperactive immune state following IL-10R blockade is enhanced by central nervous system-restricted viral infection in a disease phase-dependent manner.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Herder, Dr Vanessa
Authors: Uhde, A.-K., Herder, V., Khan, M. A., Ciurkiewicz, M., Schaudien, D., Teich, R., Floess, S., Baumgärtner, W., Huehn, J., and Beineke, A.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
Journal Name:PLoS ONE
Publisher:Public Library of Science
ISSN:1932-6203
ISSN (Online):1932-6203
Copyright Holders:Copyright © 2016 Uhde et al.
First Published:First published in PLoS ONE 11(9): e0161883
Publisher Policy:Reproduced under a Creative Commons License

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