The Toxoplasma gondii ME-49 strain upregulates levels of A20 that inhibit NE-κB activation and promotes apoptosis in human leukaemia T-cell lines

Background: Acute T-lymphocyte leukaemia is a form of haematological malignancy with abnormal activation of NE-kappa B pathway, which results in high expression of A20 and ABIN1, which constitute a negative feedback mechanism for the regulation of NE-kappa B activation. Clinical studies have found that acute T-lymphocyte leukaemia patients are susceptible to Toxoplasma gondii infection; however, the effect of T gondii on the proliferation and apoptosis of human leukaemia T-cells remains unclear. Here, we used the T gondii ME-49 strain to infect human leukaemia T-cell lines Jurkat and Molt-4, to explore the effect of T. gondii on proliferation and apoptosis, which is mediated by NE-kappa B in human leukaemia T-cells. Methods: The Tunel assay was used to detect cell apoptosis. Cell Counting Kit-8 was used to detect cell proliferation viability. The apoptosis level and the expression level of NE-kappa B related proteins in human leukaemia T-cells were detected by flow cytometry and Western blotting. Results: Western blotting analyses revealed that the T gondii ME-49 strain increased the expression of A20 and decreased both ABIN1 expression and NE-KB p65 phosphorylation. By constructing a lentiviral-mediated shRNA to knockdown the A20 gene in Jurkat T-cells and Molt-4 T-cells, the apoptosis levels of the two cell lines decreased after T gondii ME-49 infection, and levels of NE-kappa B p65 phosphorylation and ABIN1 were higher than in the non-konckdown group. After knockingdown ABIN1 gene expression by constructing the lentiviral-mediated shRNA and transfecting the recombinant expression plasmid containing the ABIN1 gene into two cell lines, apoptosis levels and cleaved caspase-8 expression increased or decreased in response to T. gondii ME-49 infection, respectively. Conclusions: Our data suggest that ABIN1 protects human leukaemia T-cells by allowing them to resist the apoptosis induced by T. gondii ME-49 and that the T. gondii ME-49 strain induces the apoptosis of human leukaemia T-cells via A20-mediated downregulation of ABIN1 expression.