Protocol for a mouse CNS demyelination model induced by a combination of HSV-1 and IL-2.
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ABSTRACT:
SUBMITTER: Hirose S
PROVIDER: S-EPMC7820129 | biostudies-literature | 2021 Mar
REPOSITORIES: biostudies-literature
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Protocol for a mouse CNS demyelination model induced by a combination of HSV-1 and IL-2.
Hirose Satoshi S Tormanen Kati K Kato Mihoko M Yu Jack J Ghiasi Homayon H
STAR protocols 20210119 1
Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system. Although viruses have been suggested to be a contributing environmental factor, conventional experimental MS mouse models do not account for this aspect. Here, we describe a mouse model to induce and evaluate demyelinating disease with both a viral and an immune component via ocular infection with a recombinant herpes simplex virus expressing murine interleukin-2. For complete details on the use and exe ...[more]
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Project description:Summary We previously reported that infection of different mouse strains with a recombinant HSV-1 expressing IL-2 (HSV-IL-2) caused CNS demyelination. Histologic examination of infected IL-2rα−/−, IL-2rβ−/−, and IL-2rγ−/− mice showed demyelination in the CNS of IL-2rα−/− and IL-2rβ−/− mice but not in the CNS of IL-2rγ−/−-infected mice. No demyelination was detected in mice infected with control virus. IL-2rγ−/− mice that lack type 2 innate lymphoid cells (ILC2s) and ILCs, play important roles in host defense and inflammation. We next infected ILC1−/−, ILC2−/−, and ILC3−/− mice with HSV-IL-2 or wild-type (WT) HSV-1. In contrast to ILC1−/− and ILC3−/− mice, no demyelination was detected in the CNS of ILC2−/−-sinfected mice. However, transfer of ILC2s from WT mice to ILC2−/− mice restored demyelination in infected recipient mice. CNS demyelination correlated with downregulation of CCL5 and CXCL10. This study demonstrates that ILC2s contribute to HSV-IL-2-induced CNS demyelination in a mouse model of multiple sclerosis. Graphical Abstract Highlights • IL-2rγ−/−, but not IL-2rα−/− or IL-2rβ−/−, mice are protected from CNS demyelination• Mice lacking ILC2s, but not ILC1s or ILC3s, are protected from CNS demyelination• Transfer of ILC2s from WT to ILC2−/− mice restore CNS demyelination to infected mice• Suppression of CCL5 and CXCL10 correlated with CNS demyelination Immunology; Neuroscience
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