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Updated: May 31, 2026
Monitoring Immune Cells Trafficking Fluorescent Prion Rods Hours after Intraperitoneal Infection
Published on: November 19, 2010
Orally administered prion protein is incorporated by m cells and spreads into lymphoid tissues with macrophages in
Ikuro Takakura1, Kohtaro Miyazawa, Takashi Kanaya
1Cellular Biology Laboratory, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan.
Abstract:
Transmissible spongiform encephalopathies are fatal neurodegenerative diseases. Infection by the oral route is assumed to be important, although its pathogenesis is not understood. Using prion protein (PrP) knockout mice, we investigated the sequence of events during the invasion of orally administered PrPs through the intestinal mucosa and the spread into lymphoid tissues and the peripheral nervous system. Orally administered PrPs were incorporated by intestinal epitheliocytes in the follicle-associated epithelium and villi within 1 hour. PrP-positive cells accumulated in the subfollicle region of Peyer's patches a few hours thereafter. PrP-positive cells spread toward the mesenteric lymph nodes and spleen after the accumulation of PrPs in the Peyer's patches. The number of PrP molecules in the mesenteric lymph nodes and spleen peaked at 2 days and 6 days after inoculation, respectively. The epitheliocytes in the follicle-associated epithelium incorporating PrPs were annexin V-positive microfold cells and PrP-positive cells in Peyer's patches and spleen were CD11b-positive and CD14-positive macrophages. Additionally, PrP-positive cells in Peyer's patches and spleen were detected in the vicinity of peripheral nerve fibers in the early stages of infection. These results indicate that orally delivered PrPs were incorporated by microfold cells promptly after challenge and that macrophages might act as a transporter of incorporated PrPs from the Peyer's patches to other lymphoid tissues and the peripheral nervous system.
Insights
Orally ingested prions rapidly enter the gut lining via microfold cells. Macrophages then transport these prions to lymphoid tissues and nerves, initiating transmissible spongiform encephalopathy infection.
Area of Science:
- Neuroscience
- Immunology
- Gastroenterology
Background:
- Transmissible spongiform encephalopathies (TSEs) are fatal neurodegenerative diseases.
- Oral infection is a significant route for TSEs, but the pathogenesis remains unclear.
Purpose of the Study:
- To elucidate the pathway of orally administered prion protein (PrP) invasion through the intestinal mucosa.
- To track the subsequent spread of PrP into lymphoid tissues and the peripheral nervous system.
Main Methods:
- Utilized prion protein (PrP) knockout mice for oral PrP administration studies.
- Employed immunohistochemistry and cell surface marker analysis (annexin V, CD11b, CD14) to identify PrP-incorporating cells.
- Examined PrP distribution in intestinal tissues, Peyer's patches, mesenteric lymph nodes, spleen, and peripheral nerves over time.
Main Results:
- Orally administered PrPs were rapidly incorporated by intestinal epitheliocytes, specifically microfold cells, within 1 hour.
- PrP-positive cells accumulated in Peyer's patches and subsequently spread to mesenteric lymph nodes and spleen.
- Macrophages (CD11b+, CD14+) were identified as the primary PrP-carrying cells in lymphoid tissues, and PrP-positive cells were found near peripheral nerves.
Conclusions:
- Microfold cells are crucial for the initial uptake of oral PrPs.
- Macrophages play a key role in transporting PrPs from Peyer's patches to other lymphoid organs and the nervous system.
- This study clarifies the early pathogenesis of oral prion disease, highlighting the intestinal immune system's involvement.
