Journal Article

Prion strain-dependent tropism is maintained between spleen and granuloma and relies on lymphofollicular structures

Moudjou, Mohammed, Martin, Davy, Béringue, Vincent, Laude, Hubert, Reine, Fabienne, Interactions hôtes-agents pathogènes [Toulouse] (IHAP) ; Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT) ; Institut National Polytechnique (Toulouse) (Toulouse INP) ; Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP) ; Université de Toulouse (UT)-Université de Toulouse (UT), Alliance Biosecure (BoHuToHu); Fondation pour la Recherche Medicale (FRM) (Equipe FRM DEQ. 20150331689), Unité de recherche Virologie et Immunologie Moléculaires (VIM (UR 0892)) ; Institut National de la Recherche Agronomique (INRA), Rezaei, Human, Al-Dybiat, Iman, Infectiologie et Santé Publique (UMR ISP) ; Institut National de la Recherche Agronomique (INRA)-Université de Tours (UT), Berthon, Patricia, Truchet, Sandrine, Sibille, Pierre, Andréoletti, Olivier, Herzog, Laetitia

2019

Overview

In peripherally acquired prion diseases, prions move through several tissues of the infected host, notably in the lymphoid tissue, long before the occurrence of neuroinvasion. Accumulation can even be restricted to the lymphoid tissue without neuroinvasion and clinical disease. Several experimental observations indicated that the presence of differentiated follicular dendritic cells (FDCs) in the lymphoid structures and the strain type are critical determinants of prion extraneural replication. In this context, the report that granulomatous structures apparently devoid of FDCs could support prion replication raised the question of the requirements for prion lymphotropism. The report also raised the possibility that nonlymphoid tissue-tropic prions could actually target these inflammatory structures. To investigate these issues, we examined the capacity of closely related prions, albeit with opposite lymphotropism (or FDC dependency), for establishment in experimentally-induced granuloma in ovine PrP transgenic mice. We found a positive correlation between the prion capacity to accumulate in the lymphoid tissue and granuloma, regardless of the prion detection method used. Surprisingly, we also revealed that the accumulation of prions in granulomas involved lymphoid-like structures associated with the granulomas and containing cells that stain positive for PrP, Mfge-8 but not CD45 that strongly suggest FDCs. These results suggest that the FDC requirement for prion replication in lymphoid/inflammatory tissues may be strain-dependent.

• Publisher: Nature Publishing Group,CCSD,Nature Publishing Group UK
• Subject: 13/51 / 14/1 / 14/63 / 631/1647/767/1972 / 64/60 / 692/420/254 / Animal biology / Animals / Antigens, Surface - metabolism / CD45 antigen / Cell differentiation / Dendritic cells / Dendritic Cells, Follicular - metabolism / Disease Models, Animal / Granuloma / Granuloma - pathology / Granulomas / Humanities and Social Sciences / Humans / Inflammation / Invasiveness / Life Sciences / Lymphoid tissue / Macrophages - metabolism / Mice / Mice, Transgenic / Milk Proteins - metabolism / multidisciplinary / Prion Diseases - pathology / Prion protein / Prion Proteins - genetics / Prion Proteins - isolation & purification / Prion Proteins - metabolism / Prion Proteins - toxicity / Prions / Protein Folding / Replication / Science / Science (multidisciplinary) / Sheep / Spleen / Spleen - cytology / Tissues / Transgenic mice / Tropism / Veterinary medicine and animal Health
• ISBN: 0004895562000