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

• Published in: Cells (Basel, Switzerland) Vol. 12; no. 14; p. 1878
• Main Authors: Kang, Sang-Gyun, Kim, Chiye, Aiken, Judd, McKenzie, Debbie
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.07.2023; MDPI
• Subjects: Alzheimer's disease; Brain research; Cell culture; Cerebellum; Cerebral cortex; Development and progression; Dexamethasone; Glial cells; Gliosis; hamster; Health aspects; hyper; Immune response; Immune status; Immunity; Immunocytochemistry; Immunomodulation; Infections; Inflammation; Innate immunity; Lipopolysaccharides; LPS; Medical research; Medicine, Experimental; Monoclonal antibodies; Neurodegenerative diseases; Neuroglia; Neuromodulation; Neurons; primary glial cultures; Prion diseases; Prion protein; Prions; Propagation; Proteins; Replication; Transgenic animals; Transmissible mink encephalopathy; Canada; United States > US; dexamethasone; drowsy; innate immunity; hamster; primary glial cultures; LPS; hyper
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells12141878

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