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Abstract Recent evidence indicates that macrophages at the maternal–fetal interface adapt to a phenotype characterized by alternative activation (M2 polarization) and exhibit immunosuppressive functions that favor the maintenance of pregnancy. The bias of M2 decidual macrophages toward M1 has been clinically linked to pregnancy-related complications, such as preeclampsia and preterm delivery. The aim of this study was to investigate the effect of Toxoplasma gondii PRU strain infection on the bias of decidual macrophage polarization and its contribution to adverse pregnancy outcomes. A mouse model with adverse pregnancy outcome was established by infection with T. gondii PRU strain and the expression levels of functional molecules in decidual macrophages of mice were measured. The results showed that T. gondii infection caused seriously adverse pregnancy outcome in mice. The placentae of infected mice showed obvious congestion and inflammatory cell infiltration. The expression of CD206, MHC-II, and arginase-1 considered as M2 markers was decreased in decidual macrophages after T. gondii infection, whereas the expression of CD80, CD86, iNOS, and cytokines TNF-α and IL-12 considered as M1 markers was increased. Furthermore, iNOS-positive expression was observed in the decidua basalis of infected mice. Our results indicated that T. gondii infection was responsible for the bias of M2 decidual macrophages toward M1, which changes the immunosuppressive microenvironment at the maternal–fetal interface and contributes to adverse pregnancy outcomes. Highlights • T. gondii infection changes functional molecule expression in decidual macrophages. • T. gondii infection affects iNOS and arginase-1 expression in decidual macrophages. • T. gondii infection alters the pattern of cytokine secretion in decidual macrophages. • T. gondii infection causes M1 polarization of decidual macrophages. • The bias of M1/M2 polarization contributes to adverse pregnancy outcomes. [ABSTRACT FROM AUTHOR]

Our current aim was to investigate whether injection of TGF-β1 played an important role in improving abnormal pregnancy outcomes with T. gondii infection and how the TGF-β1 regulated. Results showed that TGF-β1 exhibited improved pregnancy outcomes induced by T. gondii infection. dNK cytotoxicity was increased with T. gondii infection while decreased with TGF-β1 treatment. dNK cytotoxicity related NKG2D/DAP10 expression, perforin, granzyme, IFN-γ and killer subsets were all increased with T. gondii infection while decreased after TGF-β1 treatment. In addition, anti-TGF-β1 antibodies could aggregate the cytotoxicity of dNK cells and the levels of molecules above. These results indicated that TGF-β1 treatment could improve the abnormal pregnancy outcomes with T. gondii infection by decreasing the cytotoxicity of dNK cells mediated by NKG2D/DAP10 pathway and killer subset. These results suggested that TGF-β1 might be a potential immunoprotective method for the treatment of abnormal pregnancy outcomes following T. gondii infection. [ABSTRACT FROM AUTHOR]

This study aims to investigate whether IL-10 regulate decidual Treg cells apoptosis to reverse the abnormal pregnancy outcomes with Toxoplasma gondii ( T. gondii ) infection. Recombinant mouse IL-10 (rIL-10) treatment and IL-10 deficiency (IL-10 −/− ) abnormal pregnancy animal models with T. gondii infection were established. Apoptosis related molecules cleaved Caspase-3 and Caspase-8 in decidual Treg cells were examined using flow cytometry. The levels of cleaved Caspase-3 and Caspase-8 in decidual Treg cells were up-regulated with T. gondii infection. Compared to infected group, the expressions of cleaved Caspase-3 and Caspase-8 in decidual Treg cells were down-regulated in rIL-10-treated group, while up-regulated in infected IL-10 −/− group. In addition, pregnant outcomes were improved in rIL-10-treated group, while worse in IL-10 −/− group compared to infected group. These findings revealed that IL-10 reduced the decidual Treg cells apoptosis contributing to improving adverse pregnant outcomes following T. gondii infection. [ABSTRACT FROM AUTHOR]