IL-1 reprogramming of adult neural stem cells limits neurocognitive recovery after viral encephalitis by maintaining a proinflammatory state

Allison L. Soung, Veronica A. Davé, Charise Garber, Eric D. Tycksen, Lauren L. Vollmer, Robyn S. Klein

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Innate immune responses to emerging RNA viruses are increasingly recognized as having significant contributions to neurologic sequelae, especially memory disorders. Using a recovery model of West Nile virus (WNV) encephalitis, we show that, while macrophages deliver the antiviral and anti-neurogenic cytokine IL-1β during acute infection; viral recovery is associated with continued astrocyte inflammasome-mediated production of inflammatory levels of IL-1β, which is maintained by hippocampal astrogenesis via IL-1R1 signaling in neural stem cells (NSC). Accordingly, aberrant astrogenesis is prevented in the absence of IL-1 signaling in NSC, indicating that only newly generated astrocytes exert neurotoxic effects, preventing synapse repair and promoting spatial learning deficits. Ex vivo evaluation of IL-1β-treated adult hippocampal NSC revealed the upregulation of developmental differentiation pathways that derail adult neurogenesis in favor of astrogenesis, following viral infection. We conclude that NSC-specific IL-1 signaling within the hippocampus during viral encephalitis prevents synapse recovery and promotes spatial learning defects via altered fates of NSC progeny that maintain inflammation.

Original languageEnglish
Pages (from-to)383-396
Number of pages14
JournalBrain, Behavior, and Immunity
Volume99
DOIs
StatePublished - Jan 2022

Keywords

  • Adult neural stem cell
  • Astrogenesis
  • Flavivirus encephalitis
  • Interleukin-1
  • Post-infectious cognitive dysfunction
  • Spatial learning
  • Synapse elimination

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