Toxoplasma gondii suppress human cord blood cell differentiation to the NK cell population

Abstract

Background: Toxoplasma gondii is an obligate intracellular protozoan parasite that can invade all mammalian cells. It is well established that natural killer (NK) cells have critical protective roles in innate immunity during infections by intracellular pathogens. In the current study, we conducted an in vitro experiment to evaluate NK cell differentiation and activation from human umbilical cord blood mononuclear cells (UCB-MNCs) after infection with T. gondii tachyzoites. Methods: UCB-MNCs were infected by fresh tachyzoites of type I (RH) or type II (PTG) strains of T. gondii pre-expanded in mesenchymal stem cells for 2 weeks in a medium enriched with stem cell factor, Flt3, IL-2, and IL-15. Flow cytometry analysis and western blot analysis were performed to measure the CD57(+), CD56(+), and Granzyme A (GZMA). Results: Data revealed that incubation of UCB-MNCs with NK cell differentiation medium increased the CD57(+), CD56(+), and GZMA. UCB-MNCs cocultured with PTG tachyzoites showed a significant reduction of CD56(+) and GZMA, but nonsignificant changes, in the levels of CD56(+) compared to the control UCB-MNCs (p > .05). Noteworthy, 2-week culture of UCB-MNCs with type I (RH) tachyzoites significantly suppressed CD57(+), CD56(+), and GZMA, showing reduction of NK cell differentiation from cord blood cells. Conclusion: Our findings suggest that virulent T. gondii tachyzoites with cytopathic effects inhibit NK cell activation and eliminate innate immune responses during infection, and consequently enable the parasite to continue its survival in the host body.