Abstract
The early replication of some orally-acquired prion strains upon stromal-derived follicular dendritic cells (FDC) within the small intestinal Peyer’s patches is essential to establish host infection, and for the disease to efficiently spread to the brain. Factors that influence the early accumulation of prions in Peyer’s patches can directly influence disease pathogenesis. The host’s immune response to a gastrointestinal helminth infection can alter susceptibility to co-infection with certain pathogenic bacteria and viruses. Here we used the natural mouse small intestine-restricted helminth pathogen Heligmosomoides polygyrus to test the hypothesis that pathology specifically within the small intestine caused by a helminth co-infection would influence oral prion disease pathogenesis. When mice were co-infected with prions on d 8 after H. polygyrus infection the early accumulation of prions within Peyer’s patches was reduced and survival times significantly extended. Natural prion susceptible hosts such as sheep, deer and cattle are regularly exposed to gastrointestinal helminth parasites. Our data suggest that co-infections with small intestine-restricted helminth pathogens may be important factors that influence oral prion disease pathogenesis.
Highlights
Prion infections cause chronic neurodegenerative diseases in humans and animals for which there are no treatments
C57BL/6J mice were orally infected with 200 H. polygyrus L3 larvae by gavage and faecal egg burdens measured at intervals afterwards to monitor the magnitude of the parasite infection
Histopathological analysis of inflammatory cell infiltrate and changes to the intestinal architecture confirmed the presence of detectable pathology within the small intestine by 8 dpi with H. polygyrus, and was significantly greater in the duodenum by 14 dpi (Fig. 1B,C)
Summary
Prion infections cause chronic neurodegenerative diseases in humans and animals for which there are no treatments. Aggregations of PrPSc, abnormally folded isoforms of the host-encoded cellular prion protein (PrPC), accumulate in the affected tissues of prion disease infected hosts and are considered to constitute the major component of the infectious agent[1,2,3] Many prion strains such as natural sheep scrapie, bovine spongiform encephalopathy (BSE) in cattle and chronic wasting disease (CWD) in cervid species can be orally acquired. The incidence of clinical cases of vCJD in humans has been much lower than originally estimated despite the probable widespread exposure of the UK population to BSE-contaminated food in the 1980s This implies that factors in addition to host PRNP genotype (which encodes PrPC) and prion agent strain can influence an individual’s susceptibility to oral prion infection. These data are essential for the identification of important factors can that influence the risk of oral prion disease transmission and to help design effective intervention and control strategies
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