Acanthamoeba interactions with the blood-brain barrier under dynamic fluid flow

James Edwards-Smallbone, Richard J. Pleass, Naveed A. Khan, Robin J. Flynn

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

Acanthamoeba granulomatous encephalitis (AGE), caused by Acanthamoeba castellanii, is a fatal infection of immunocompromised individuals. The pathogenesis of blood-brain barrier (BBB) breach remains unknown. Using a novel in vitro BBB infection model under flow conditions, demonstrates that increases in flow rates lead to decreased binding of A. castellanii to host cells. This is a distinct departure from previous findings under static conditions. However, similarly to static conditions binding of A. castellanii to host cells is host mannose dependent. Disruption of the host cell monolayer was independent of amoeba binding, but dependent on secreted serine proteases. For the first time we report the binding dynamics of A. castellanii under physiological conditions, showing that BBB disruption is not directly linked to binding, instead it is reliant on secreted proteases. Our results offer a platform on which therapies designed at modulating physiological parameters can improve the outcome of infection with A. castellanii.

Original languageEnglish
Pages (from-to)367-372
Number of pages6
JournalExperimental Parasitology
Volume132
Issue number3
DOIs
Publication statusPublished - Nov 2012
Externally publishedYes

Keywords

  • Acanthamoeba
  • Amoeba
  • Blood-brain barrier
  • Flow system
  • Mannose binding protein

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