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

Intracellular microorganisms have to rely on the integrity of their host ce lls to persist. We, therefore, investigated the effect of infections with d ifferent Toxoplasma gondii strains on apoptosis of human-derived HL-60 cell s at the single cell level. Infection with either mouse-avirulent (NTE stra in) or virulent parasites (RH strain) did not induce apoptosis of HL-60 cel ls as compared to uninfected controls. In contrast, treatment with actinomy cin 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 w as 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 b y living, but not necessarily replicating T. gondii may facilitate parasite survival and persistence within its host cell.