Intact interleukin-10 receptor signaling protects from hippocampal damage elicited by experimental neurotropic virus infection of SJL mice

Uhde, A.-K. et al. (2018) Intact interleukin-10 receptor signaling protects from hippocampal damage elicited by experimental neurotropic virus infection of SJL mice. Scientific Reports, 8, 6106. (doi: 10.1038/s41598-018-24378-z) (PMID:29666403) (PMCID:PMC5904160)

Abstract

Theiler’s murine encephalomyelitis virus (TMEV) infection represents an experimental mouse model to study hippocampal damage induced by neurotropic viruses. IL-10 is a pleiotropic cytokine with profound anti-inflammatory properties, which critically controls immune homeostasis. In order to analyze IL-10R signaling following virus-induced polioencephalitis, SJL mice were intracerebrally infected with TMEV. RNA-based next generation sequencing revealed an up-regulation of Il10, Il10rα and further genes involved in IL-10 downstream signaling, including Jak1, Socs3 and Stat3 in the brain upon infection. Subsequent antibody-mediated blockade of IL-10R signaling led to enhanced hippocampal damage with neuronal loss and increased recruitment of CD3+ T cells, CD45R+ B cells and an up-regulation of Il1α mRNA. Increased expression of Tgfβ and Foxp3 as well as accumulation of Foxp3+ regulatory T cells and arginase-1+ macrophages/microglia was detected in the hippocampus, representing a potential compensatory mechanism following disturbed IL-10R signaling. Additionally, an increased peripheral Chi3l3 expression was found in spleens of infected mice, which may embody reactive regulatory mechanisms for prevention of excessive immunopathology. The present study highlights the importance of IL-10R signaling for immune regulation and its neuroprotective properties in the context of an acute neurotropic virus infection.

• Item Type: Articles
• Additional Information: The study was supported by the Deutsche Forschungsgemeinschaft (DFG, BE 4200/1-2; HU 1300/5-2) and in part by the Niedersachsen-Research Network on Neuroinfectiology (N-RENNT) of the Ministry of Science and Culture of Lower Saxony. This publication was supported by the Deutsche Forschungsgemeinschaft (DFG) and University of Veterinary Medicine Hannover, Foundation within the funding programme Open Access Publishing.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Herder, Dr Vanessa
• Authors: Uhde, A.-K., Ciurkiewicz, M., Herder, V., Khan, M. A., Hensel, N., Claus, P., Beckstette, M., Teich, R., Floess, S., Baumgärtner, W., Jung, K., Huehn, J., and Beineke, A.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
• Journal Name: Scientific Reports
• Publisher: Nature Research
• ISSN: 2045-2322
• ISSN (Online): 2045-2322
• Copyright Holders: Copyright © 2018 The Authors
• First Published: First published in Scientific Reports 8: 6106
• Publisher Policy: Reproduced under a Creative Commons License