title: A lympho-follicular microenvironment is required for pathological prion protein deposition in chronically inflamed tissues from scrapie-affected sheep.
abstract: In sheep scrapie, pathological prion protein (PrP(Sc)) deposition occurs in the lymphoreticular and central nervous systems. We investigated PrP(Sc) distribution in scrapie-affected sheep showing simultaneous evidence of chronic lymphofollicular, lymphoproliferative/non-lymphofollicular, and/or granulomatous inflammations in their mammary gland, lung, and ileum. To do this, PrP(Sc) detection was carried out via immunohistochemistry and Western Blotting techniques, as well as through inflammatory cell immunophenotyping. Expression studies of gene coding for biological factors modulating the host's inflammatory response were also carried out. We demonstrated that ectopic PrP(Sc) deposition occurs exclusively in the context of lymphofollicular inflammatory sites, inside newly formed and well-organized lymphoid follicles harboring follicular dendritic cells. On the contrary, no PrP(Sc) deposition was detected in granulomas, even when they were closely located to newly formed lymphoid follicles. A significantly more consistent expression of lymphotoxin α and β mRNA was detected in lymphofollicular inflammation compared to the other two types, with lymphotoxin α and β signaling new lymphoid follicles' formation and, likely, the occurrence of ectopic PrP(Sc) deposition inside them. Our findings suggest that, in sheep co-affected by scrapie and chronic inflammatory conditions, only newly formed lymphoid follicles provide a suitable micro-environment that supports the scrapie agent's replication in inflammatory sites, with an increased risk of prion shedding through body secretions/excretions.
authors: Dipartimento di Sanità Animale, Istituto Zooprofilattico Sperimentale della Sardegna, Sassari, Italy.
authors: Caterina
authors: C
authors: Maestrale
authors: Giovanni
authors: G
authors: Di Guardo
authors: Maria Giovanna
authors: MG
authors: Cancedda
authors: Giuseppe
authors: G
authors: Marruchella
authors: Mariangela
authors: M
authors: Masia
authors: Stefania
authors: S
authors: Sechi
authors: Simonetta
authors: S
authors: Macciocu
authors: Cinzia
authors: C
authors: Santucciu
authors: Mara
authors: M
authors: Petruzzi
authors: Ciriaco
authors: C
authors: Ligios
mesh_terms: D000818:Animals; D020566:Dendritic Cells, Follicular / Q000276:immunology / Q000473:pathology*; D005260:Female; D015870:Gene Expression; D007082:Ileum / Q000276:immunology / Q000473:pathology*; D007249:Inflammation; D008168:Lung / Q000276:immunology / Q000473:pathology*; D008221:Lymphoid Tissue / Q000276:immunology / Q000473:pathology*; D008233:Lymphotoxin-alpha / Q000235:genetics / Q000276:immunology; D053308:Lymphotoxin-beta / Q000235:genetics / Q000276:immunology; D008321:Mammary Glands, Animal / Q000276:immunology / Q000473:pathology*; D018620:PrPSc Proteins / Q000235:genetics* / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012608:Scrapie / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D034561:Sheep, Domestic
chemical_list: D008233:Lymphotoxin-alpha; D053308:Lymphotoxin-beta; D018620:PrPSc Proteins; D012333:RNA, Messenger
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