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ASC- and caspase-1-deficient C57BL/6 mice do not develop demyelinating disease after infection with Theiler's murine encephalomyelitis virus

Scientific reports, 2023-07, Vol.13 (1), p.10960-10960, Article 10960 [Peer Reviewed Journal]

2023. The Author(s). ;The Author(s) 2023. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. ;The Author(s) 2023 ;ISSN: 2045-2322 ;EISSN: 2045-2322 ;DOI: 10.1038/s41598-023-38152-3 ;PMID: 37414913

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  • Title:
    ASC- and caspase-1-deficient C57BL/6 mice do not develop demyelinating disease after infection with Theiler's murine encephalomyelitis virus
  • Author: Li, Dandan ; Bühler, Melanie ; Runft, Sandra ; Gerold, Gisa ; Marek, Katarzyna ; Baumgärtner, Wolfgang ; Strowig, Till ; Gerhauser, Ingo
  • Subjects: Adaptor proteins ; Antiviral activity ; Apoptosis ; Caspase-1 ; Demyelinating diseases ; Demyelination ; Encephalomyelitis ; Gene expression ; IL-1β ; Immunodeficiency ; Immunohistochemistry ; Inflammasomes ; Inflammation ; Interleukin 18 ; Pattern recognition receptors ; Polioencephalomyelitis ; Viruses ; β-Interferon
  • Is Part Of: Scientific reports, 2023-07, Vol.13 (1), p.10960-10960, Article 10960
  • Description: Theiler's murine encephalomyelitis virus (TMEV) induces an acute polioencephalomyelitis and a chronic demyelinating leukomyelitis in SJL mice. C57BL/6 (B6) mice generally do not develop TMEV-induced demyelinating disease (TMEV-IDD) due to virus elimination. However, TMEV can persist in specific immunodeficient B6 mice such as IFNβ mice and induce a demyelinating process. The proinflammatory cytokines IL-1β and IL-18 are activated by the inflammasome pathway, which consists of a pattern recognition receptor molecule sensing microbial pathogens, the adaptor molecule Apoptosis-associated speck-like protein containing a CARD (ASC), and the executioner caspase-1. To analyze the contribution of the inflammasome pathway to the resistance of B6 mice to TMEV-IDD, ASC- and caspase-1-deficient mice and wild type littermates were infected with TMEV and investigated using histology, immunohistochemistry, RT-qPCR, and Western Blot. Despite the antiviral activity of the inflammasome pathway, ASC- and caspase-1-deficient mice eliminated the virus and did not develop TMEV-IDD. Moreover, a similar IFNβ and cytokine gene expression was found in the brain of immunodeficient mice and their wild type littermates. Most importantly, Western Blot showed cleavage of IL-1β and IL-18 in all investigated mice. Consequently, inflammasome-dependent activation of IL-1β and IL-18 does not play a major role in the resistance of B6 mice to TMEV-IDD.
  • Publisher: England: Nature Publishing Group
  • Language: English
  • Identifier: ISSN: 2045-2322
    EISSN: 2045-2322
    DOI: 10.1038/s41598-023-38152-3
    PMID: 37414913
  • Source: PubMed Central
    SWEPUB Freely available online
    ProQuest Central
    DOAJ Directory of Open Access Journals
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