Acanthamoeba castellanii induces host cell death via a phosphatidylinositol 3-kinase-dependent mechanism
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Updated: Aug 18, 2026

LPS and ATP-induced Death of PMA-differentiated THP-1 Macrophages and its Validation
Published on: May 3, 2024
James Sissons1, Kwang Sik Kim, Monique Stins
1School of Biological and Chemical Sciences, Birkbeck, College, University of London, London WC1E 7HX, England, United Kingdom.
Abstract:
Granulomatous amoebic encephalitis due to Acanthamoeba castellanii is a serious human infection with fatal consequences, but it is not clear how the circulating amoebae interact with the blood-brain barrier and transmigrate into the central nervous system. We studied the effects of an Acanthamoeba encephalitis isolate belonging to the T1 genotype on human brain microvascular endothelial cells, which constitute the blood-brain barrier. Using an apoptosis-specific enzyme-linked immunosorbent assay, we showed that Acanthamoeba induces programmed cell death in brain microvascular endothelial cells. Next, we observed that Acanthamoeba specifically activates phosphatidylinositol 3-kinase. Acanthamoeba-mediated brain endothelial cell death was abolished using LY294002, a phosphatidylinositol 3-kinase inhibitor. These results were further confirmed using brain microvascular endothelial cells expressing dominant negative forms of phosphatidylinositol 3-kinase. This is the first demonstration that Acanthamoeba-mediated brain microvascular endothelial cell death is dependent on phosphatidylinositol 3-kinase.
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