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Prion pathogenesis is unaltered following down-regulation of SIGN-R1

Barry M Bradford1, Karen L Brown1, Neil A Mabbott1

  • 1The Roslin Institute and R(D)SVS, University of Edinburgh, Easter Bush, Midlothian EH25 9RG, UK.

Virology
|August 15, 2016
PubMed

Insights

SIGN-R1, a molecule on spleen macrophages, does not impact prion disease progression. This finding suggests SIGN-R1 is not essential for prion transport to the brain after peripheral exposure.

Area of Science:

  • Neuroscience
  • Immunology
  • Pathology

Background:

  • Prion diseases are fatal neurodegenerative disorders caused by abnormal prion protein accumulation.
  • Prions replicate in lymphoid tissues on follicular dendritic cells (FDC) before brain infection.
  • Splenic marginal zone macrophages expressing SIGN-R1 are crucial for prion delivery to FDC.

Purpose of the Study:

  • To investigate the role of SIGN-R1 in prion disease pathogenesis.
  • To determine if SIGN-R1 is essential for prion transport and FDC accumulation.

Main Methods:

  • Transiently down-regulated SIGN-R1 expression in mice prior to prion exposure.
  • Assessed early prion accumulation on splenic FDC.
  • Monitored prion spread to the brain.

Main Results:

  • Down-regulating SIGN-R1 did not affect early prion accumulation on splenic FDC.
  • SIGN-R1 down-regulation did not alter prion spread to the brain.
  • The presence of SIGN-R1 on marginal zone macrophages is not rate-limiting for prion disease.

Conclusions:

  • SIGN-R1 expression by marginal zone macrophages is not critical for peripheral prion disease pathogenesis.
  • This study clarifies the role of SIGN-R1 in the initial stages of prion infection.
Keywords:
Follicular dendritic cellMacrophageMarginal zonePrionsSpecific intercellular adhesion molecule-3-grabbing non-integrin related 1 (SIGN-R1)SpleenTransmissible spongiform encephalopathies

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