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Updated: Aug 17, 2026
Monitoring Immune Cells Trafficking Fluorescent Prion Rods Hours after Intraperitoneal Infection
Published on: November 19, 2010
Role of gut macrophages in mice orally contaminated with scrapie or BSE
Thomas Maignien1, Monjed Shakweh, Pilar Calvo
1CEA, Service de Neurovirologie, CRSSA, B.P.6, Fontenay-aux-Roses Cedex, France.
Abstract:
While there is a growing consensus on the understanding of the propagation pathways after oral infection of transmissible spongiform encephalopathy (TSE) agents and even if the central role of follicular dendritic cells is identified, little is known about the key players in the first steps of the infection and about the site of the disease development. We investigated the role of gut macrophages, which are capable of capturing aggregates of the prion protein. PLGA particles containing clodronate were designed in order to be orally administered and to target Peyer's patches for inducing gut-associated macrophages suicide in mice. Mice were subsequently infected with scrapie or BSE by the oral route. It was found that the efficacy of macrophage suppression in the Peyer's patches correlated well with an earlier appearance of PrPres in these formations and with a higher amount of PrPres at a later stage of the infection. Thus, the capture of infectious particles that have crossed the epithelial gut barrier and their elimination by macrophages seems to be a key event to restrict the amount of agent initiating the infection.
Insights
Gut macrophages play a crucial role in limiting prion disease by capturing infectious agents after oral exposure. Suppressing these macrophages accelerates prion accumulation, highlighting their importance in early infection control.
Area of Science:
- Neuroscience
- Immunology
- Infectious Diseases
Background:
- Transmissible spongiform encephalopathy (TSE) propagation pathways are increasingly understood, with follicular dendritic cells identified as key players.
- However, the initial infection steps and early disease development sites remain largely unknown.
- Gut macrophages are implicated in capturing prion protein aggregates.
Purpose of the Study:
- To investigate the role of gut macrophages in the initial stages of oral prion infection.
- To determine if targeting gut-associated macrophages impacts prion disease progression.
Main Methods:
- Oral administration of PLGA particles containing clodronate to induce apoptosis in gut-associated macrophages in mice.
- Oral infection of treated mice with scrapie or Bovine spongiform encephalopathy (BSE) agents.
- Monitoring the appearance and quantity of PrPres (protease-resistant prion protein) in Peyer's patches.
Main Results:
- Macrophage suppression in Peyer's patches correlated with an earlier PrPres appearance.
- Higher amounts of PrPres were observed at later stages following macrophage suppression.
- Efficacy of macrophage suppression directly influenced prion accumulation.
Conclusions:
- Gut macrophages are critical in capturing and potentially eliminating infectious prion particles that breach the gut barrier.
- Elimination of these particles by macrophages is a key event in restricting the initial infectious load.
- Targeting gut macrophages could be a strategy to limit prion disease initiation.
