Detection of PrPBSE and prion infectivity in the ileal Peyer\u2019s patch of young calves as early as 2\xa0months after oral challenge with classical bovine spongiform encephalopathy

Ivett Ackermann,Reiner Ulrich,Olanrewaju I Fatola,Markus Keller,James C Shawulu,Anne Balkema-Buschmann,Kerstin Tauscher,Paul Brown,Martin H Groschup

doi:10.1186/s13567-017-0495-5

Abstract

In classical bovine spongiform encephalopathy (C-BSE), an orally acquired prion disease of cattle, the ileal Peyer’s patch (IPP) represents the main entry port for the BSE agent. In earlier C-BSE pathogenesis studies, cattle at 4–6 months of age were orally challenged, while there are strong indications that the risk of infection is highest in young animals. In the present study, unweaned calves aged 4–6 weeks were orally challenged to determine the earliest time point at which newly formed PrPBSE and BSE infectivity are detectable in the IPP. For this purpose, calves were culled 1 week as well as 2, 4, 6 and 8 months post-infection (mpi) and IPPs were examined for BSE infectivity using a bovine PrP transgenic mouse bioassay, and for PrPBSE by immunohistochemistry (IHC) and protein misfolding cyclic amplification (PMCA) assays. For the first time, BSE prions were detected in the IPP as early as 2 mpi by transgenic mouse bioassay and PMCA and 4 mpi by IHC in the follicular dendritic cells (FDCs) of the IPP follicles. These data indicate that BSE prions propagate in the IPP of unweaned calves within 2 months of oral uptake of the agent.

Highlights

Transmissible spongiform encephalopathies (TSEs), or prion diseases, are fatal neurodegenerative disorders including scrapie, bovine spongiform encephalopathy (BSE) and chronic wasting disease (CWD) in animals and Creutzfeldt-Jakob disease (CJD) in humans
The ileal Peyer’s patch (IPP), representing the gutassociated lymphoid tissue (GALT) of the ileum, has been postulated to function as the primary site of entry for the BSE agent in cattle, as PrPBSE and BSE infectivity have been detected from 4 mpi in this location [3,4,5,6]
Animals To warrant the worst case scenario of the supposedly highest prion susceptibility, unweaned calves aged 4–6 weeks were chosen for oral BSE challenge. 20 unweaned Simmental mixed male and female calves were orally challenged with classical BSE using a 100 g dose of a brainstem homogenate pool of >50 clinically diseased cattle

Summary

Introduction

Transmissible spongiform encephalopathies (TSEs), or prion diseases, are fatal neurodegenerative disorders including scrapie, bovine spongiform encephalopathy (BSE) and chronic wasting disease (CWD) in animals and Creutzfeldt-Jakob disease (CJD) in humans. In previous studies PrPBSE has been detected in the IPP follicles from 4 mpi and in the enteric nervous system (ENS) of the distal ileum as early as 16 mpi [3, 4]. In those earlier reports, neither infectivity nor PrPBSE was detectable prior to 4 mpi, and the earliest sampled time point 1 mpi was tested negative [3, 4]. The time point of initial accumulation of PrPBSE and BSE infectivity in the IPP was not yet determined

Methods

Results

Conclusion