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

2.50
Hdl Handle:
http://hdl.handle.net/10033/621368
Title:
Intact interleukin-10 receptor signaling protects from hippocampal damage elicited by experimental neurotropic virus infection of SJL mice.
Authors:
Uhde, Ann-Kathrin; Ciurkiewicz, Malgorzata; Herder, Vanessa; Khan, Muhammad Akram; Hensel, Niko; Claus, Peter; Beckstette, Michael; Teich, René; Floess, Stefan; Baumgärtner, Wolfgang; Jung, Klaus; Huehn, Jochen ( 0000-0001-8071-1379 ) ; Beineke, Andreas
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.
Affiliation:
Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany.
Citation:
Intact interleukin-10 receptor signaling protects from hippocampal damage elicited by experimental neurotropic virus infection of SJL mice. 2018, 8 (1):6106 Sci Rep
Journal:
Scientific reports
Issue Date:
17-Apr-2018
URI:
http://hdl.handle.net/10033/621368
DOI:
10.1038/s41598-018-24378-z
PubMed ID:
29666403
Type:
Article
Language:
en
ISSN:
2045-2322
Appears in Collections:
publications of the division experimentelle Immunologie (EXIM)

Full metadata record

DC FieldValue Language
dc.contributor.authorUhde, Ann-Kathrinen
dc.contributor.authorCiurkiewicz, Malgorzataen
dc.contributor.authorHerder, Vanessaen
dc.contributor.authorKhan, Muhammad Akramen
dc.contributor.authorHensel, Nikoen
dc.contributor.authorClaus, Peteren
dc.contributor.authorBeckstette, Michaelen
dc.contributor.authorTeich, Renéen
dc.contributor.authorFloess, Stefanen
dc.contributor.authorBaumgärtner, Wolfgangen
dc.contributor.authorJung, Klausen
dc.contributor.authorHuehn, Jochenen
dc.contributor.authorBeineke, Andreasen
dc.date.accessioned2018-05-09T12:14:35Z-
dc.date.available2018-05-09T12:14:35Z-
dc.date.issued2018-04-17-
dc.identifier.citationIntact interleukin-10 receptor signaling protects from hippocampal damage elicited by experimental neurotropic virus infection of SJL mice. 2018, 8 (1):6106 Sci Repen
dc.identifier.issn2045-2322-
dc.identifier.pmid29666403-
dc.identifier.doi10.1038/s41598-018-24378-z-
dc.identifier.urihttp://hdl.handle.net/10033/621368-
dc.description.abstractTheiler'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.en
dc.language.isoenen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.titleIntact interleukin-10 receptor signaling protects from hippocampal damage elicited by experimental neurotropic virus infection of SJL mice.en
dc.typeArticleen
dc.contributor.departmentHelmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany.en
dc.identifier.journalScientific reportsen
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