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Toll-like receptor-mediated immune response inhibits prion propagation

Prion diseases are progressive neurodegenerative disorders affecting humans and various mammals. The prominent neuropathological change in prion diseases is neuroinflammation characterized by activation of neuroglia surrounding prion deposition. The cause and effect of this cellular response, howeve...

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Published in:Glia 2016-06, Vol.64 (6), p.937-951
Main Authors: Kang, Sang-Gyun, Kim, Chiye, Cortez, Leonardo M., Carmen Garza, María, Yang, Jing, Wille, Holger, Sim, Valerie L., Westaway, David, McKenzie, Debbie, Aiken, Judd
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cited_by cdi_FETCH-LOGICAL-c4943-95d5a269d39900334aee8a1affca5dd27a563d57d843699fb8f9097c18e479b93
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container_title Glia
container_volume 64
creator Kang, Sang-Gyun
Kim, Chiye
Cortez, Leonardo M.
Carmen Garza, María
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Wille, Holger
Sim, Valerie L.
Westaway, David
McKenzie, Debbie
Aiken, Judd
description Prion diseases are progressive neurodegenerative disorders affecting humans and various mammals. The prominent neuropathological change in prion diseases is neuroinflammation characterized by activation of neuroglia surrounding prion deposition. The cause and effect of this cellular response, however, is unclear. We investigated innate immune defenses against prion infection using primary mixed neuronal and glial cultures. Conditional prion propagation occurred in glial cultures depending on their immune status. Preconditioning of the cells with the toll‐like receptor (TLR) ligand, lipopolysaccharide, resulted in a reduction in prion propagation, whereas suppression of the immune responses with the synthetic glucocorticoid, dexamethasone, increased prion propagation. In response to recombinant prion fibrils, glial cells up‐regulated TLRs (TLR1 and TLR2) expression and secreted cytokines (tumor necrosis factor‐α, interleukin‐1β, interleukin‐6, granulocyte‐macrophage colony‐stimulating factor, and interferon‐β). Preconditioning of neuronal and glial cultures with recombinant prion fibrils inhibited prion replication and altered microglial and astrocytic populations. Our results provide evidence that, in early stages of prion infection, glial cells respond to prion infection through TLR‐mediated innate immunity. GLIA 2016;64:937–951 Main Points Preconditioning of glial cells with a sterile ligand, recombinant prion fibril, inhibits prion propagation. Prion‐sensing is mediated by toll‐like receptors triggering protective innate immune responses in early stage of prion infection.
doi_str_mv 10.1002/glia.22973
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ispartof Glia, 2016-06, Vol.64 (6), p.937-951
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subjects Animals
Cells, Cultured
Creutzfeldt-Jakob disease
Cytokines
Cytokines - metabolism
glial cells
Granulocyte-Macrophage Colony-Stimulating Factor - metabolism
immune competent cells
Immunity, Innate - immunology
Infections
innate immunity
Interleukin-1beta - metabolism
Mice
Neuroglia - immunology
Neuroglia - metabolism
Pneumoviridae
prion defense
Prions - immunology
Prions - metabolism
Propagation
Toll-Like Receptors - metabolism
Tumor Necrosis Factor-alpha - metabolism
title Toll-like receptor-mediated immune response inhibits prion propagation
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