Open AccessA Lympho-Follicular Microenvironment Is Required for Pathological Prion Protein Deposition in Chronically Inflamed Tissues from Scrapie-Affected Sheep
Author(s) -
Caterina Maestrale,
Giovanni Di Guardo,
Maria Giovanna Cancedda,
Giuseppe Marruchella,
Mariangela Masia,
Stefania Sechi,
Simonetta Macciocu,
Cinzia Santucciu,
Mara Petruzzi,
Ciriaco Ligios
Publication year - 2013
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0062830
Subject(s) - scrapie , lymphotoxin , biology , pathology , follicular dendritic cells , inflammation , ectopic expression , lymphatic system , immunohistochemistry , context (archaeology) , proinflammatory cytokine , immunology , immune system , medicine , gene , t cell , prion protein , paleontology , biochemistry , disease , antigen presenting cell
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.