Innate Immune Status of Glia Modulates Prion Propagation in Early Stage of Infection

Prion diseases are progressive neurodegenerative disorders affecting humans and various mammals. The prominent neuropathological change in prion-affected brains is neuroinflammation, histopathologically characterized by reactive gliosis surrounding prion deposition. cause effect of these cellular responses still unclear. Here we investigate the impact innate immune on replication using vitro cell culture models. Hamster-adapted transmissible mink encephalopathy prions, hyper (HY) drowsy (DY) strains, were assayed for accumulation pathogenic protein (PrPSc) primary glial cultures derived from 8-day-old hamster pups. kinetics PrPSc largely depended strain brain regions where cells originated. Glial cerebellum susceptible to HY, but resistant DY as determined western blot analysis, immunocytochemistry, animal bioassay. cerebral cortex were, however, refractory both strains. was affected modulators. Priming with lipopolysaccharide decreased replication, whereas pre-treatment dexamethasone, inhibiting immunity, increased susceptibility infection. Our results suggest that neuroinflammation resulting infection a response resolve and/or prevent propagation brain. It implies therapeutic potential modulation early stages disease.