Prior murine neurotropic coronavirus infection ameliorates experimental autoimmune encephalitis.

BACKGROUND Central nervous system (CNS) infections contribute to the development of neuroinflammation and neurodegenerative diseases. However, the mechanisms underlying the correlation between CNS infection and subsequent inflammatory course remain largely unknown. METHODS Here, we addressed this question by infecting mice with a sublethal dose of a well-studied neurotropic coronavirus, mouse hepatitis virus (MHV), and investigated the effects of infection on the subsequent induction of a mouse multiple sclerosis (MS) model (myelin oligodendrocyte glycoprotein 35-55 (MOG35-55) peptide-induced experimental autoimmune encephalitis (EAE)). RESULTS Unexpectedly, C57BL/6J mice that recovered from MHV infection showed alleviated clinical signs of induced EAE. Mechanistically, this protection is mediated by a novel CNS-resident Foxp3+ CD8 T cell population induced by interleukin (IL)-10, which was secreted by myeloid cells that infiltrated the MHV-infected CNS as part of the MHV-specific immune response. These Foxp3+ CD8 T cells ameliorated EAE severity by decreasing the quantity and function of autoreactive CD4 and CD8 T cell infiltrating CNS independent of antigen specificity, as well as by inhibiting the activation of microglia accumulating in the affected spinal cords (SCs). The persistence of these Foxp3+ CD8 T cells in the CNS may contribute to the long-term post-acute sequelae of infection. CONCLUSION This study reveals a novel post-infectious anti-inflammatory milieu that develops in MHV-infected CNS of MHV and leads to the generation of Foxp3+ CD8 regulatory T cells, thereby diminishing the progression of subsequent autoimmune disease.

• Publication year

  2025

• Venue

  Journal of Autoimmunity

• Publication date

  2025-11-24

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1016/j.jaut.2025.103504PMID 41289822PMCID PMC12688706
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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