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.
Subject(s)
Cell Differentiation , Fetal Blood , Killer Cells, Natural , Toxoplasma , Humans , Killer Cells, Natural/immunology , Fetal Blood/cytology , Fetal Blood/immunology , Fetal Blood/parasitology , Cell Differentiation/immunology , Toxoplasma/immunology , Cells, Cultured , Toxoplasmosis/immunology , Toxoplasmosis/parasitology , Immunity, Innate , Lymphocyte Activation/immunology , Leukocytes, Mononuclear/immunologyABSTRACT
Toxoplasma gondii is an intracellular protozoan parasite that can remarkably infect, survive, and replicate in almost all mammalian cells and can cause severe neurological and ocular damage in immunocompromised individuals. It is known that Natural Killer cells (NK cells), as a type of cytotoxic lymphocyte, have critical protective roles in innate immunity during the T. gondii infection through releasing interferon gamma (IFN-γ). Interleukin 12 (IL-12) is a pivotal critical cytokine for the generation of IFN-γ-producing NK cells. Several studies have shown cytokines' impact on NK cell activation; and IL-2 has an important role with a potent stimulatory factor for NK cells. In this review, we summarized the mechanism of interleukin-12 production stimulation by T. gondii tachyzoites and discussed several factors affecting this mechanism.
