Invasion by Toxoplasma gondii protects human-derived HL-60 cells from actinomycin D-induced apoptosis

Abstract

Intracellular microorganisms have to rely on the integrity of their host cells to persist. We, therefore, investigated the effect of infections with different Toxoplasma gondii strains on apoptosis of human-derived HL-60 cells at the single cell level. Infection with either mouse-avirulent (NTE strain) or virulent parasites (RH strain) did not induce apoptosis of HL-60 cells as compared to uninfected controls. In contrast, treatment with actinomycin D (act D) led to apoptosis in 15–25% of the cells. However, concomitant infection with T. gondii clearly abrogated act D-induced apoptosis. This was especially apparent in those host cells that were actually infected; in these parasite-positive cells the rate of apoptosis decreased by 82.8±4.3% (mean±SEM, P=0.017, Student's t-test) and 91.7±3.4% (P=0.024) after infection with either the NTE or the RH strain, respectively. Inhibition of host cell apoptosis was similarly observed in cells which had been invaded by UV-irradiated, non-replicating parasites (P=0.001, Student's t-test). However, incubation with heat-killed parasites or T. gondii lysates did not abrogate act D-induced apoptosis. In conclusion, inhibition of apoptosis by living, but not necessarily replicating T. gondii may facilitate parasite survival and persistence within its host cell.