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A lympho-follicular microenvironment is required for pathological prion protein deposition in chronically inflamed tissues from scrapie-affected sheep.

Maestrale C, Di Guardo G, Cancedda MG, Marruchella G, Masia M, Sechi S, Macciocu S, Santucciu C, Petruzzi M, Ligios C - PLoS ONE (2013)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Dipartimento di Sanità Animale, Istituto Zooprofilattico Sperimentale della Sardegna, Sassari, Italy.

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.

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Inflammatory lesions patterns in ovine mammary glands.Micrographs show the inflammatory lesions’ morphology in mammary glands from sheep concurrently affected by scrapie and mastitis. Representative patterns of lymphofollicular (A), granulomatous (B), and lymphoproliferative/non-lymphofollicular (C) mastitis. A histologically normal ovine mammary gland is also shown (D). Hematoxylin-eosin (H&E) stain. Scale bar = 100 µm.
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pone-0062830-g001: Inflammatory lesions patterns in ovine mammary glands.Micrographs show the inflammatory lesions’ morphology in mammary glands from sheep concurrently affected by scrapie and mastitis. Representative patterns of lymphofollicular (A), granulomatous (B), and lymphoproliferative/non-lymphofollicular (C) mastitis. A histologically normal ovine mammary gland is also shown (D). Hematoxylin-eosin (H&E) stain. Scale bar = 100 µm.

Mentions: Gross and histopathological investigations yielded a total number of 27 sheep affected by scrapie and associated lesions indicative of chronic inflammation in mammary glands, lungs, and ileum (Table 1). Histologically, chronically inflamed mammary glands showed 3 distinct morphological lesion patterns, which were classified as lymphofollicular, lymphoproliferative/non-lymphofollicular, and granulomatous mastitis (Figure 1). The first two lesional patterns indicated MVV as their cause, with this viral agent being detected by RT-PCR. Furthermore, in all cases of lymphoproliferative/non-lymphofollicular mastitis, we observed variable numbers of lymphocytes and plasma cells infiltrating, along with a few macrophages, the interlobular and interalveolar spaces. As far as the lymphofollicular lesion pattern is specifically concerned, this was characterized by a number of lymphoid cell aggregates containing GCs resembling secondary follicles.


A lympho-follicular microenvironment is required for pathological prion protein deposition in chronically inflamed tissues from scrapie-affected sheep.

Maestrale C, Di Guardo G, Cancedda MG, Marruchella G, Masia M, Sechi S, Macciocu S, Santucciu C, Petruzzi M, Ligios C - PLoS ONE (2013)

Inflammatory lesions patterns in ovine mammary glands.Micrographs show the inflammatory lesions’ morphology in mammary glands from sheep concurrently affected by scrapie and mastitis. Representative patterns of lymphofollicular (A), granulomatous (B), and lymphoproliferative/non-lymphofollicular (C) mastitis. A histologically normal ovine mammary gland is also shown (D). Hematoxylin-eosin (H&E) stain. Scale bar = 100 µm.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3643908&req=5

pone-0062830-g001: Inflammatory lesions patterns in ovine mammary glands.Micrographs show the inflammatory lesions’ morphology in mammary glands from sheep concurrently affected by scrapie and mastitis. Representative patterns of lymphofollicular (A), granulomatous (B), and lymphoproliferative/non-lymphofollicular (C) mastitis. A histologically normal ovine mammary gland is also shown (D). Hematoxylin-eosin (H&E) stain. Scale bar = 100 µm.
Mentions: Gross and histopathological investigations yielded a total number of 27 sheep affected by scrapie and associated lesions indicative of chronic inflammation in mammary glands, lungs, and ileum (Table 1). Histologically, chronically inflamed mammary glands showed 3 distinct morphological lesion patterns, which were classified as lymphofollicular, lymphoproliferative/non-lymphofollicular, and granulomatous mastitis (Figure 1). The first two lesional patterns indicated MVV as their cause, with this viral agent being detected by RT-PCR. Furthermore, in all cases of lymphoproliferative/non-lymphofollicular mastitis, we observed variable numbers of lymphocytes and plasma cells infiltrating, along with a few macrophages, the interlobular and interalveolar spaces. As far as the lymphofollicular lesion pattern is specifically concerned, this was characterized by a number of lymphoid cell aggregates containing GCs resembling secondary follicles.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Dipartimento di Sanità Animale, Istituto Zooprofilattico Sperimentale della Sardegna, Sassari, Italy.

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.

Show MeSH
Related in: MedlinePlus