Accelerated onset of CNS prion disease in mice co-infected with a gastrointestinal helminth pathogen during the preclinical phase

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Abstract

Prion infections in the central nervous system (CNS) can cause extensive
neurodegeneration. Systemic inflammation can affect the progression of some
neurodegenerative disorders. Therefore, we used the gastrointestinal helminth
pathogen Trichuris muris to test the hypothesis that a chronic systemic inflammatory response to a gastrointestinal infection would similarly affect CNS prion disease pathogenesis. Mice were injected with prions directly into the CNS and subsequently orally co-infected with T. muris before the onset of clinical signs. We show that coinfection with a low dose of T. muris that leads to the development of a chronic T 30 helper cell type 1-polarized systemic immune response accelerated the onset of clinical prion disease. In contrast, co-infection with a high dose of T. muris that induces a T helper cell type 2-polarized immune response did not affect prion disease pathogenesis. The reduced survival times in mice co-infected with a low dose of T. muris on d 105 after CNS prion infection coincided with enhanced astrocyte activation in the brain during the preclinical phase. These data aid our understanding of how systemic inflammation may augment the progression of neurodegeneration in the CNS.
Original languageEnglish
Article number4554 (2020)
JournalScientific Reports
Volume10
DOIs
Publication statusPublished - 12 Mar 2020

Keywords

  • Astrocyte
  • Encephalopathy
  • Infection
  • Neuroimmunology
  • Parasite host response

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