NOX4 activation is involved in ROS-dependent Jurkat T-cell death induced by Entamoeba histolytica

Abstract

AIMS: Entamoeba histolytica can induce host cell death through induction of various intracellular signalling pathways. The responses triggered by E. histolytica are closely associated with tissue pathogenesis and immune evasion. Although E. histolytica can induce reactive oxygen species (ROS) in host cells, which NADPH oxidase (NOX) isoform contributes to amoeba-triggered Jurkat T-cell death is unclear. In this study, we investigated the signalling role of NOX4-derived ROS in E. histolytica-induced Jurkat T-cell death process.

METHODS AND RESULTS: In resting-state Jurkat T cells, NOX4 is strongly expressed. When Jurkat T cells were incubated with live E. histolytica trophozoites, intracellular ROS was significantly increased compared to cells incubated with medium alone. E. histolytica-induced ROS production was inhibited by pretreating Jurkat T cells with a NOX inhibitor. In addition, pretreating Jurkat T cells with a NOX inhibitor (Diphenyleneiodonium chloride) effectively blocked E. histolytica-induced phosphatidylserine (PS) exposure and DNA fragmentation of host cells. Moreover, siRNA-mediated knockdown of NOX4 protein expression in Jurkat T cells prevented E. histolytica-induced ROS generation and DNA fragmentation.

CONCLUSION: These results suggest that NOX4 has a critical role in ROS-dependent cell death process in Jurkat T cells induced by E. histolytica.