Role of gut macrophages in mice orally contaminated with scrapie or BSE.
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.
Maignien
Thomas
T
CEA, Service de Neurovirologie, CRSSA, B.P.6, Fontenay-aux-Roses Cedex, France.
Shakweh
Monjed
M
Calvo
Pilar
P
Marcé
Dominique
D
Salès
Nicole
N
Fattal
Elias
E
Deslys
Jean-Philippe
JP
Couvreur
Patrick
P
Lasmezas
Corinne Ida
CI
D000818:Animals; D002417:Cattle; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004002:Clodronic Acid; D004064:Digestive System / Q000473:pathology*; D004339:Drug Compounding; D016643:Encephalopathy, Bovine Spongiform / Q000473:pathology*; D005456:Fluorescent Dyes; D007150:Immunohistochemistry; D019344:Lactic Acid; D008264:Macrophages / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D010316:Particle Size; D010581:Peyer's Patches / Q000473:pathology; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D012235:Rhodamines; D012608:Scrapie / Q000473:pathology*
D005456:Fluorescent Dyes; D011108:Polymers; D012235:Rhodamines; D004002:Clodronic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid