Complement facilitates early prion pathogenesis.

Détails

ID Serval
serval:BIB_18258
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Complement facilitates early prion pathogenesis.
Périodique
Nature Medicine
Auteur(s)
Klein M.A., Kaeser P.S., Schwarz P., Weyd H., Xenarios I., Zinkernagel R.M., Carroll M.C., Verbeek J.S., Botto M., Walport M.J., Molina H., Kalinke U., Acha-Orbea H., Aguzzi A.
ISSN
1078-8956
Statut éditorial
Publié
Date de publication
2001
Peer-reviewed
Oui
Volume
7
Numéro
4
Pages
488-492
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't Publication Status: ppublish
Résumé
New-variant Creutzfeldt-Jakob disease and scrapie are typically initiated by extracerebral exposure to the causative agent, and exhibit early prion replication in lymphoid organs. In mouse scrapie, depletion of B-lymphocytes prevents neuropathogenesis after intraperitoneal inoculation, probably due to impaired lymphotoxin-dependent maturation of follicular dendritic cells (FDCs), which are a major extracerebral prion reservoir. FDCs trap immune complexes with Fc-gamma receptors and C3d/C4b-opsonized antigens with CD21/CD35 complement receptors. We examined whether these mechanisms participate in peripheral prion pathogenesis. Depletion of circulating immunoglobulins or of individual Fc-gamma receptors had no effect on scrapie pathogenesis if B-cell maturation was unaffected. However, mice deficient in C3, C1q, Bf/C2, combinations thereof or complement receptors were partially or fully protected against spongiform encephalopathy upon intraperitoneal exposure to limiting amounts of prions. Splenic accumulation of prion infectivity and PrPSc was delayed, indicating that activation of specific complement components is involved in the initial trapping of prions in lymphoreticular organs early after infection.
Mots-clé
Animals, Base Sequence, Brain/metabolism, Brain/pathology, Complement System Proteins/deficiency, Complement System Proteins/genetics, DNA Primers/genetics, Disease Models, Animal, Humans, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Prion Diseases/etiology, Prion Diseases/immunology, Prions/metabolism, Receptors, Complement/deficiency, Receptors, Complement/genetics, Scrapie/etiology, Scrapie/immunology, Spleen/immunology, Spleen/metabolism, Time Factors
Pubmed
Web of science
Création de la notice
19/11/2007 12:12
Dernière modification de la notice
20/08/2019 12:48
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