Infected splenic dendritic cells are sufficient for prion transmission to the CNS in mouse scrapie

J Clin Invest. 2001 Sep;108(5):703-8. doi: 10.1172/JCI13155.

Abstract

Transmissible spongiform encephalopathies display long incubation periods at the beginning of which the titer of infectious agents (prions) increases in peripheral lymphoid organs. This "replication" leads to a progressive invasion of the CNS. Follicular dendritic cells appear to support prion replication in lymphoid follicles. However, the subsequent steps of neuroinvasion remain obscure. CD11c(+) dendritic cells, an unrelated cell type, are candidate vectors for prion propagation. We found a high infectivity titer in splenic dendritic cells from prion-infected mice, suggesting that dendritic cells carry infection. To test this hypothesis, we injected RAG-1(0/0) mice intravenously with live spleen cell subsets from scrapie-infected donors. Injection of infected dendritic cells induced scrapie without accumulation of prions in the spleen. These results suggest that CD11c(+) dendritic cells can propagate prions from the periphery to the CNS in the absence of any additional lymphoid element.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adoptive Transfer
  • Animals
  • Dendritic Cells / chemistry
  • Dendritic Cells / physiology*
  • Dendritic Cells / transplantation
  • Genes, RAG-1
  • Integrin alphaXbeta2 / analysis
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • PrPSc Proteins / analysis
  • Prions / pathogenicity*
  • Scrapie / immunology
  • Scrapie / pathology
  • Scrapie / transmission*
  • Spleen / anatomy & histology
  • Spleen / pathology*

Substances

  • Integrin alphaXbeta2
  • PrPSc Proteins
  • Prions