Scrapie infection can be established readily through skin scarification in immunocompetent but not immunodeficient mice

Taylor, David; McConnell, I.; Fraser, H.

doi:10.1099/0022-1317-77-7-1595

Cited by 84 publications

(64 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Infection of sheep and cattle by TSE agents occurs through the oral route although scarification of the skin and infection of (damaged) mucous membranes/conjunctiva are suggested as alternative routes of infection [45,58,61]. In scrapie, the infectious agent is present in the environment and taken up orally during grazing on scrapie contaminated pastures [8,13,14].…”

Section: Crossing the Mucosal Barriermentioning

confidence: 99%

TSE pathogenesis in cattle and sheep

2008

View full text Add to dashboard Cite

-Many studies have been undertaken in rodents to study the pathogenesis of transmissible spongiform encephalopathies (TSE). Only a few studies have focused on the pathogenesis of bovine spongiform encephalopathy (BSE) and scrapie in their natural hosts. In this review, we summarize the most recent insights into the pathogenesis of BSE and scrapie starting from the initial uptake of TSE agents and crossing of the gut epithelium. Following replication in the gut-associated lymphoid tissues (GALT), TSE agents spread to the enteric nervous system (ENS) of the gut. Infection is then carried through the efferent fibers of the post-ganglionic neurons of the parasympathetic and sympathetic nervous system to the pre-ganglionic neurons in the medulla oblongata of the brain and the thoracic segments of the spinal cord. The differences between the pathogenesis of BSE in cattle and scrapie in sheep are discussed as well as the possible existence of additional pathogenetic routes.

show abstract

Section: Crossing the Mucosal Barriermentioning

confidence: 99%

TSE pathogenesis in cattle and sheep

2008

View full text Add to dashboard Cite

show abstract

“…TSE diseases target and affect the CNS and usually present with characteristic deposition of a protease-resistant isoform of the host-encoded protein PrP C . TSEs are naturally acquired peripherally (Taylor et al, 1996;Bartz et al, 2003) and are associated with prolonged incubation periods, during which the infectious agent travels to the CNS (Kimberlin and Walker, 1980;Glatzel et al, 2002). Precisely which cells are involved in TSE neuroinvasion is currently unknown, though the infectious agent has been traced through the peripheral nervous system (PNS) (Schulz-Schaeffer et al, 2000;McBride et al, 2001) and Schwann cells have been implicated in this process (Follet et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Dramatic Reduction of PrP^CLevel and Glycosylation in Peripheral Nerves following PrP Knock-Out from Schwann Cells Does Not Prevent Transmissible Spongiform Encephalopathy Neuroinvasion

Bradford¹,

Tuzi²,

Feltri³

et al. 2009

J. Neurosci.

View full text Add to dashboard Cite

Expression of the prion protein (PrP C ) is a requirement for host susceptibility to the transmissible spongiform encephalopathies (TSEs) and thought to be necessary for the replication and transport of the infectious agent. The mechanism of TSE neuroinvasion is not fully understood, although the routing of infection has been mapped through the peripheral nervous system (PNS) and Schwann cells have been implicated as a potential conduit for transport of the TSE infectious agent. To address whether Schwann cells are a requirement for spread of the TSE agent from the site of infection to the CNS, PrP C expression was selectively removed from Schwann cells in vivo. This dramatically reduced total PrP C within peripheral nerves by 90%, resulting in the selective loss of glycosylated PrP C species. Despite this, 139A and ME7 mouse-passaged scrapie agent strains were efficiently replicated and transported to the CNS following oral and intraperitoneal exposure. Thus, the myelinating glial cells within the PNS do not appear to play a significant role in TSE neuroinvasion.

show abstract

“…For example, the consumption of BSE-contaminated meat products by humans is most likely responsible for the emergence of vCJD (7,22). Although many natural TSE infections are likely to be acquired orally, studies in mice show that skin scarification is also an effective means of scrapie transmission (51). This suggests some natural TSE cases might be transmitted through skin lesions in the mouth (3) or through sites of skin trauma during close contact with infected animals.…”

mentioning

confidence: 99%

Neuroinvasion by Scrapie following Inoculation via the Skin Is Independent of Migratory Langerhans Cells

Mohan

Bruce

Mabbott

2005

J Virol

View full text Add to dashboard Cite

Many natural transmissible spongiform encephalopathy (TSE) infections are likely to be acquired peripherally, and studies in mice show that skin scarification is an effective means of scrapie transmission. After peripheral exposure, TSE agents usually accumulate in lymphoid tissues before spreading to the brain. The mechanisms of TSE transport to lymphoid tissues are not known. Langerhans cells (LCs) reside in the epidermis and migrate to the draining lymph node after encountering antigen. To investigate the potential role of LCs in scrapie transportation from the skin, we utilized mouse models in which their migration was blocked either due to CD40 ligand deficiency (CD40L ؊/؊ mice) or after caspase-1 inhibition. We show that the early accumulation of scrapie infectivity in the draining lymph node and subsequent neuroinvasion was not impaired in mice with blocked LC migration. Thus, LCs are not involved in TSE transport from the skin. After intracerebral inoculation with scrapie, wild-type mice and CD40L ؊/؊ mice develop clinical disease with similar incubation periods. However, after inoculation via skin scarification CD40L ؊/؊ mice develop disease significantly earlier than do wild-type mice. The shorter incubation period in CD40L ؊/؊ mice is unexpected and suggests that a CD40L-dependent mechanism is involved in impeding scrapie pathogenesis. In vitro studies demonstrated that LCs have the potential to acquire and degrade protease-resistant prion protein, which is thought to be a component of the infectious agent. Taken together, these data suggest that LCs are not involved in scrapie transport to draining lymphoid tissues but might have the potential to degrade scrapie in the skin.

show abstract

Scrapie infection can be established readily through skin scarification in immunocompetent but not immunodeficient mice

Cited by 84 publications

References 16 publications

TSE pathogenesis in cattle and sheep

TSE pathogenesis in cattle and sheep

Dramatic Reduction of PrP^CLevel and Glycosylation in Peripheral Nerves following PrP Knock-Out from Schwann Cells Does Not Prevent Transmissible Spongiform Encephalopathy Neuroinvasion

Neuroinvasion by Scrapie following Inoculation via the Skin Is Independent of Migratory Langerhans Cells

Contact Info

Product

Resources

About

Scrapie infection can be established readily through skin scarification in immunocompetent but not immunodeficient mice

Cited by 84 publications

References 16 publications

TSE pathogenesis in cattle and sheep

TSE pathogenesis in cattle and sheep

Dramatic Reduction of PrPCLevel and Glycosylation in Peripheral Nerves following PrP Knock-Out from Schwann Cells Does Not Prevent Transmissible Spongiform Encephalopathy Neuroinvasion

Neuroinvasion by Scrapie following Inoculation via the Skin Is Independent of Migratory Langerhans Cells

Contact Info

Product

Resources

About

Dramatic Reduction of PrP^CLevel and Glycosylation in Peripheral Nerves following PrP Knock-Out from Schwann Cells Does Not Prevent Transmissible Spongiform Encephalopathy Neuroinvasion