Enhanced enteric invasion of scrapie agents into the villous columnar epithelium via maternal immunoglobulin.
Transmissible spongiform encephalopathies (TSE) are caused by dietary oral exposure to infectious prion proteins (PrPSc); however, the mechanism behind the uptake of PrPSc in the intestines is poorly understood. In addition, epidemiological studies of BSE showed that most cattle are exposed to the agents in the first 6 months of life, during the suckling and weaning periods. In the present study, to elucidate the enteric invasion mechanism of prions and to investigate the age-dependent transmission mechanism suggested by epidemiological studies, wild-type and SCID mice were orally administered brain homogenate from scrapie (Tsukuba 1)-infected mice during the suckling and weaning stages, before being analyzed histopathologically. PrPSc was found to be incorporated into the villous columnar epithelial cells and was also detected in the villous lacteal of 15-day-old suckling mice. However, no such uptake of PrPSc was observed in the weaned mice at 25-days-old. Four different strains of mice were tested. There was no mouse strain difference in the frequency of PrPSc positive columnar epithelial cells. In addition, the uptake of PrPSc in suckling SCID mice lacking maternal antibodies was significantly lower than that in the wild-type suckling mice, and the uptake of PrPSc was enhanced by dilution with purified IgG. In the present study, it was suggested that the weaning period and maternal immunoglobulin are important risk factors for the oral transmission of PrPSc.
Graduate School of Agricultural and Life Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
Yasuhisa
Y
Ano
Akikazu
A
Sakudo
Ryuta
R
Uraki
Yukita
Y
Sato
Jyuri
J
Kono
Katsuaki
K
Sugiura
Takashi
T
Yokoyama
Shigeyoshi
S
Itohara
Hiroyuki
H
Nakayama
Masayoshi
M
Yukawa
Takashi
T
Onodera
D000284:Administration, Oral; D000367:Age Factors; D000818:Animals; D000833:Animals, Suckling; D001923:Brain Chemistry; D002417:Cattle; D018562:Disease Transmission, Infectious; D054884:Host-Pathogen Interactions; D007136:Immunoglobulins / Q000276:immunology / Q000378:metabolism*; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D018620:PrPSc Proteins / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism*; D017096:Prion Diseases / Q000209:etiology / Q000276:immunology / Q000378:metabolism*
D007136:Immunoglobulins; D018620:PrPSc Proteins