Myeloid-derived suppressor cells (MDSCs) play a crucial role in maintaining maternal-fetal tolerance for pregnancy by expressing immune suppressive molecules, such as indoleamine 2,3-dioxygenase (IDO), arginase-1 (Arg-1) and IL-10. The expression of IDO was downregulated in dDCs after Toxoplasma gondii (T. gondii) infection. However, whether T. gondii affected IDO expression in dMDSCs and then induced dNK cells dysfunction were still unclear. The human infected dMDSCs were co-cultured with purified dNK cells in vitro. Results showed that IDO expression in infected dMDSCs was significantly increased in the mRNA level but obviously decreased in the protein level. The transcriptional levels of IDO in dMDSCs were up-regulated through STAT3/p52-RelB pathway and IDO expression was decreased by degradation due to the increase of SOCS3 expression induced by T. gondii infection. In vivo, we found that adverse pregnancy outcomes of IDO−/− infected mice by T. gondii infection were more severe than those of WT mice and were significantly improved after treatment with exogenous kynurenine (Kyn). The reduction of IDO in dMDSCs induced by T. gondii infection lastly resulted in the downregulation of TGF-β and IL-10 expression in dNK cells through Kyn/AhR/SP1 signaling pathway, eventually leading to the dysfunction of dNK cells.