4.5 Article

Endothelial cells are a replicative niche for entry of Toxoplasma gondii to the central nervous system

Journal

NATURE MICROBIOLOGY
Volume 1, Issue 3, Pages -

Publisher

NATURE PUBLISHING GROUP
DOI: 10.1038/NMICROBIOL.2016.1

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Funding

  1. German Research Foundation (DFG) [KO 4609-1/1]
  2. National Institutes of Health [NIH AI 41158, NIH NS065116, NIH AI041930]
  3. American Heart Association [14BGIA20380675, 15POST25550021]
  4. University of Arizona
  5. BIO5 Institute
  6. NIH [S10RR027128]
  7. School of Veterinary Medicine
  8. University of Pennsylvania
  9. Commonwealth of Pennsylvania

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An important function of the blood-brain barrier is to exclude pathogens from the central nervous system, but some microorganisms benefit from the ability to enter this site. It has been proposed that Toxoplasma gondii can cross biological barriers as a motile extracellular form that uses transcellular or paracellular migration, or by infecting a host cell that then crosses the blood-brain barrier. Unexpectedly, analysis of acutely infected mice revealed significant numbers of free parasites in the blood and the presence of infected endothelial cells in the brain vasculature. The use of diverse transgenic parasites combined with reporter mice and intravital imaging demonstrated that replication in and lysis of endothelial cells precedes invasion of the central nervous system, and highlight a novel mechanism for parasite entry to the central nervous system.

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