Scrapie-Specific Pathology of Sheep Lymphoid Tissues

Abstract

Transmissible spongiform encephalopathies (TSEs) or prion diseases often result in accumulation of disease-associated PrP (PrPd) in the lymphoreticular system (LRS), specifically in association with follicular dendritic cells (FDCs) and tingible body macrophages (TBMs) of secondary follicles. We studied the effects of sheep scrapie on lymphoid tissue in tonsils and lymph nodes by light and electron microscopy. FDCs of sheep were grouped according to morphology as immature, mature or regressing. Scrapie was associated with FDC dendrite hypertrophy and electron dense deposit or vesicles. PrPd was located using immunogold labelling at the plasmalemma of FDC dendrites and, infrequently, mature B cells. Abnormal electron dense deposits surrounding FDC dendrites were identified as immunoglobulins suggesting that excess immune complexes are retained and are indicative of an FDC dysfunction. Within scrapie-affected lymph nodes, macrophages outside the follicle and a proportion of germinal centre TBMs accumulated PrPd within endosomes and lysosomes. In addition, TBMs showed PrPd in association with the cell membrane, non-coated pits and vesicles, and also with discrete, large and random endoplasmic reticulum networks, which co-localised with ubiquitin. These observations suggest that PrPd is internalised via the caveolin-mediated pathway, and causes an abnormal disease-related alteration in endoplasmic reticulum structure. In contrast to current dogma, this study shows that sheep scrapie is associated with cytopathology of germinal centres, which we attribute to abnormal antigen complex trapping by FDCs and abnormal endocytic events in TBMs. The nature of the sub-cellular changes in FDCs and TBMs differs from those of scrapie infected neurones and glial cells suggesting that different PrPd/cell membrane interactions occur in different cell types.

B Cells and Platelets Harbor Prion Infectivity in the Blood of Deer Infected with Chronic Wasting Disease

“…Subsequent studies utilizing confocal microscopy confirmed an association between PrP RES and immune cells (FDCs, tingible body macrophages, and B cells) and extended the repertoire of prion diseases with lymphoid involvement to include CWD and vCJD (42,55,60,66,67). B cells have been associated with PrP RES transport and/or deposition within the lymphoid system (9,10,18,22,23,32,43,56,64,66,81). The present study supports this contention in demonstrating that MAb 2-104 ϩ primarily B cells harvested from peripheral blood or retropharyngeal lymph nodes contain sufficient infectious prions to transmit CWD to native or transgenic hosts.…”

“…The presence of PrP RES in lymph node tingible body macrophages of scrapie-infected sheep (1,31,40,56) and CWD-infected deer (66) led us to investigate the possibility that circulating CD14 ϩ monocytes may contain infectious prions capable of transmitting disease. Somewhat to our surprise, the results indicated that in CWD this is not the case.…”

Features of follicular dendritic cells in ovine pharyngeal tonsil: An in vivo and in vitro study in the context of scrapie pathogenesis

“…In fact, cellular prion protein is also expressed by B and T cells, platelets, erythrocytes, monocytes and dendritic cells with significant differences across species and in terms of the state of maturation of the cells (Aguzzi and Heikenwalder, 2005;Nuvolone et al, 2009). Recently, an ultrastructural analysis in situ with an immunogold labelling of the pathogen protein showed the presence of PrPd on both the FDC cytoplasmic extensions and the B lymphocyte membranes (McGovern and Jeffrey, 2007). Nevertheless, B lymphocytes are unlikely to represent a major site for prion replication (Montrasio et al, 2001).…”

Lesion Profiling and Subcellular Prion Localization of Cervid Chronic Wasting Disease in Domestic Cats

“…22 In CWD, evidence of the in vivo plasticity of the species barrier has been illustrated by successful interspecies infection of cattle, sheep, goats, ferret, mink, squirrel monkeys, transgenic mice, and recently domestic cats. 19,39 However, despite these studies, the entirety of the natural CWD host range has yet to be fully clarified. Relevant to the work described here is the potential role that sympatric species, including large cats, might play in the spread of CWD, particularly in light of studies providing compelling evidence that mountain lions ( Puma concolor ) selectively prey on CWD-infected deer.…”