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Toxoplasma gondii infection during pregnancy can result in adverse pregnancy outcomes. Previously, we have reported that these outcomes are associated with the impaired function of decidual Treg cells; however, the detailed mechanisms involved were unclear. It has been reported that the suppressive capacity of Treg cells is dependent on PD-1 expression. The present study explored the role of decidual PD-1+ Treg cell function in adverse pregnancy outcomes due to T. gondii infection. Toxoplasma gondii–infected pregnant mice were sacrificed on gestational day 14 and their pregnancy outcomes were observed. The expression of PD-1 on decidual Treg cells and expressions of Foxp3, CTLA-4, TGF-β, and IL-10 on decidual PD-1+ and PD-1− Treg cells were determined using flow cytometry. The results showed that the expression of PD-1 on decidual Treg cells was clearly higher in the T. gondii–infected mice than in the normal mice. Meanwhile, the expressions of Foxp3, CTLA-4, TGF-β, and IL-10 on decidual PD-1+ Treg cells were higher in the infected mice than in the normal mice. The expressions were higher in decidual PD1+ Treg cells than in PD-1− Treg cells in the infected mice. However, these expressions on PD-1− Treg cells did not significantly differ between the infected and normal mice. Nonetheless, the absolute percentages of decidual PD-1+ Treg cells decreased significantly in the infected mice compared with those in the normal mice. These results suggest that T. gondii infection mainly influences the function of decidual PD-1+ Treg cells, which would result in an insufficiently immunotolerant microenvironment and consequently in adverse pregnancy outcomes. [ABSTRACT FROM AUTHOR]

There is crosstalk between decidual natural killer (dNK) cells and decidual dendritic cells (dDCs) that promotes tolerance of trophoblast cells carrying paternally derived antigens. In the present study, we report that infection of CD1c dDCs with Toxoplasma gondii enhanced gamma interferon (IFN-γ) production by dNK cells in co-culture. The enhancement of IFN-γ production was induced by cytokine IL-12 which increased obviously in co-culture of dDCs with dNK cells following T. gondii infection, and this enhancement largely abrogated when cells were cultured in the presence of an anti-IL-12 antibody. The expression of KIR2DL4 and NKG2D on dNK cells was increased after T. gondii infection, and higher expression of NKG2D was induced by co-cultured dDCs. Neutralization of IL-12 decreased NKG2D expression on dNK cells. Furthermore, dDCs with T. gondii infection increased the cytotoxicity of co-cultured dNK cells against K562 target cells, which was mediated by activating receptor of NKG2D. Thus, T. gondii infection of dDCs enhanced dNK cell IFN-γ production and NKG2D expression, and then led to increased cytotoxicity of dNK cells. The up-regulated dNK cell cytotoxicity at the maternal-fetal interface may contribute to abnormal pregnancy outcomes caused by T. gondii infection in early pregnancy. [ABSTRACT FROM AUTHOR]

The aim of this study were to demonstrate the effects of Yellow fluorescent protein- Toxoplasma gondii infection on the NK-92 cells co-cultured with BeWo cells in vitro and to verify the implications upon adverse pregnancy outcome. There are four groups including NK-92 cells infected or uninfected with T. gondii, and NK-92 cells co-cultured with BeWo cells in the presence or absent of T. gondii infection. Cells were observed by fluorescence microscope at 12, 24, 36, 48, and 60 h after infection. Levels of inhibitory receptors killer immunoglobulin-like receptor (KIR)2DL4 and ILT-2 expressed on NK-92 cells, and their common ligand HLA-G expressed on BeWo cells were measured by real-time PCR and flow cytometry in all groups. Levels of KIR2DL4, ILT-2 and HLA-G increased at 12, 24, 36, and 48 h, while decreased at 60 h in all T. gondii-infected groups compared with their parallel control groups, respectively. KIR2DL4 and ILT-2 expression in co-culture groups with infection were higher than those in infected NK-92 groups at 12, 24, 36, and 48 h, while there were no significant differences at 60 h. The expression of the two inhibitory receptors was correlated with HLA-G expression in infected co-culture groups. The changes of inhibitory receptors on NK-92 cells and their common ligand HLA-G on BeWo cells with T. gondii infection might contribute to the occurrence of adverse pregnancy outcome. [ABSTRACT FROM AUTHOR]