Follicular dendritic cells and dissemination of Creutzfeldt-Jakob disease

L. Manuelidis, I. Zaitsev, P. Koni, Z. Y. Lu, R. A. Flavell, W. Fritch

Research output: Contribution to journalArticle

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Abstract

The contribution of immune system cells to the propagation of transmissible encephalopathies is not well understood. To determine how follicular dendritic cells (FDC) may act, we challenged lymphotoxin β null and wild-type (wt) controls with a Creutzfeldt-Jakob disease (CJD) agent. There was only a small difference in incubation time to clinical disease even after peripheral challenge with low infectious doses (31 in a total of 410 days). Brain pathology with extensive microglial infiltration, identified by keratan sulfate, as well as astrocytic hypertrophy, was also equivalent in all groups despite the fact that null mice had neither FDC nor splenic metallophilic macrophages that filter particulate antigen. Because FDC accumulate pathologic prion protein (PrP) in infected but not wt mice, we studied the cellular distribution of PrP by confocal microscopy. The majority of pathologic PrP collected on the plasma membrane of FDC, as identified by the Ca+2-binding protein S100A. This surface distribution suggested that agent aggregated with pathologic PrP might spread by cell-to-cell contacts. While several types of leukocytes may be involved in agent dissemination, cells of myeloid lineage were found to be infectious. Moreover, perivascular tracks of microglia and abnormal PrP after intraperitoneal inoculation were consistent with hematogenous spread. In summary, FDC are not required for CJD agent spread from the periphery, although FDC may enhance spread through surface accumulation of pathologic PrP. While it is still not clear where the infectious agent replicates, macrophages can sequester appreciable levels of infectivity and hence act as reservoirs for prolonged latent infection.

Original languageEnglish (US)
Pages (from-to)8614-8622
Number of pages9
JournalJournal of Virology
Volume74
Issue number18
DOIs
StatePublished - Sep 13 2000

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Follicular Dendritic Cells
Creutzfeldt-Jakob Syndrome
prions
dendritic cells
macrophages
lymphotoxin
Macrophages
cells
Keratan Sulfate
Lymphotoxin-alpha
encephalopathy
mice
neuroglia
Microglia
Brain Diseases
Cell Lineage
hypertrophy
Confocal Microscopy
Hypertrophy
immune system

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Manuelidis, L., Zaitsev, I., Koni, P., Lu, Z. Y., Flavell, R. A., & Fritch, W. (2000). Follicular dendritic cells and dissemination of Creutzfeldt-Jakob disease. Journal of Virology, 74(18), 8614-8622. https://doi.org/10.1128/JVI.74.18.8614-8622.2000

Follicular dendritic cells and dissemination of Creutzfeldt-Jakob disease. / Manuelidis, L.; Zaitsev, I.; Koni, P.; Lu, Z. Y.; Flavell, R. A.; Fritch, W.

In: Journal of Virology, Vol. 74, No. 18, 13.09.2000, p. 8614-8622.

Research output: Contribution to journalArticle

Manuelidis, L, Zaitsev, I, Koni, P, Lu, ZY, Flavell, RA & Fritch, W 2000, 'Follicular dendritic cells and dissemination of Creutzfeldt-Jakob disease', Journal of Virology, vol. 74, no. 18, pp. 8614-8622. https://doi.org/10.1128/JVI.74.18.8614-8622.2000
Manuelidis L, Zaitsev I, Koni P, Lu ZY, Flavell RA, Fritch W. Follicular dendritic cells and dissemination of Creutzfeldt-Jakob disease. Journal of Virology. 2000 Sep 13;74(18):8614-8622. https://doi.org/10.1128/JVI.74.18.8614-8622.2000
Manuelidis, L. ; Zaitsev, I. ; Koni, P. ; Lu, Z. Y. ; Flavell, R. A. ; Fritch, W. / Follicular dendritic cells and dissemination of Creutzfeldt-Jakob disease. In: Journal of Virology. 2000 ; Vol. 74, No. 18. pp. 8614-8622.
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