Acanthamoeba castellanii induces host cell death via a phosphatidylinositol 3-kinase-dependent mechanism.
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.
Sissons
James
J
School of Biological and Chemical Sciences, Birkbeck, College, University of London, London WC1E 7HX, England, United Kingdom.
Kim
Kwang Sik
KS
Stins
Monique
M
Jayasekera
Samantha
S
Alsam
Selwa
S
Khan
Naveed Ahmed
NA
D048248:Acanthamoeba castellanii / Q000472:pathogenicity*; D000562:Amebiasis / Q000469:parasitology / Q000503:physiopathology; D000818:Animals; D017209:Apoptosis; D001812:Blood-Brain Barrier; D001921:Brain / Q000098:blood supply*; D002478:Cells, Cultured; D020808:Central Nervous System Protozoal Infections / Q000469:parasitology / Q000503:physiopathology; D004660:Encephalitis / Q000469:parasitology / Q000503:physiopathology; D042783:Endothelial Cells / Q000201:enzymology / Q000469:parasitology* / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology / Q000469:parasitology; D006801:Humans; D008833:Microcirculation / Q000201:enzymology / Q000469:parasitology* / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*
D019869:Phosphatidylinositol 3-Kinases