[PD-1/PD-L1 expression and its interaction with interferon-γ in -infected mice at middle and late pregnancy].

Objective: To explore the dynamic expression of programmed cell death-1 (PD-1) and its ligand PD-L1 at the maternal-fetal interface of mice post-infection with at early pregnancy and examine its interaction with interferon-γ (IFN-γ).

Methods: A total of 20 mice at day 0 of pregnancy were randomly assigned into 4 groups, including the 12-day pregnancy control group (12 dpn group), 12-day pregnancy and infection group (12 dpi group), 18-day pregnancy control group (18 dpn group) and 18-day pregnancy and infection group (18 dpi group), respectively. On the 6th day of the pregnancy, mice in the 12 dpi and 18 dpi groups were injected intraperitoneally with 150 tachyzoites of the PRU strain, while mice in the 12 dpn and 18 dpn groups were injected with the same volume of PBS. All mice in the four groups were sacrificed on 12th and 18 day of the pregnancy, and the number of placenta and fetus was counted and the weight of placenta and fetus was measured. Then, the placental and uterine tissues of the pregnant mice in each group were sampled for pathological examinations. The expression of , , surface antigen and genes was quantified using a quantitative real-time PCR (qPCR) assay, and the correlation between and expression was examined. In addition, the 12 dpn group, 12 dpi group, 18 dpn group, 18 dpi group, PBS negative control of the 12 pdi group and PBS negative control of the 18 dpi group were assigned, and the expression was determined in the uterine and placenta tissues of the pregnant mice.

Results: Adverse pregnant outcomes were seen in mice in the 12 dpi and 18 dpi groups, including placental dysplasia and fetal maldevelopment, and the placental weights and fetal body weights were significantly lower in mice in the 12 dpi and 18 dpi groups than those in the 12 dpn and 18 dpn groups ( = 5.52, 11.44, 12.63 and 11.67, all < 0.01). The histopathological examinations showed that the decidua and junctional regions of the placental tissues were loosely connected in the 12 dpi and 18 dpi groups, and a large number of inflammatory cells infiltration and congestion were seen in the placental and uterine tissues. qPCR assay detected significant differences in , , and expression in the placental and uterine tissues among the 12 dpn, 12 dpi, 18 dpn and 18 dpi groups ( = 22.48, 51.23, 9.61, 47.49, 16.08, 21.52, 28.66 and 238.90, all < 0.05), and the , , and expression was all significantly higher in the placental and uterine tissues of mice in the 12 dpi group than in the 12 dpn group (all values < 0.05). The and expression was significantly lower in the placental tissues of mice in the 18 dpi group than in the 18 dpn group (all values < 0.05), and the and expression was significantly higher in the placental and uterine tissues of mice in the 18 dpi group than in the 18 dpn group (all values < 0.05), while the and expression was significantly lower in the placental and uterine tissues of mice in the 18 dpi group than in the 12 dpi group (all values < 0.05). Immunohistochemical staining showed PD-1 expression in the inflammatory cells of the placental tissues of mice in the 12 dpi group, and no apparent PD-1 expression in the 18 dpi group, while strongly positive PD-1 expression was found in the uterine epithelium of mice in the 12 dpi group, and mildly strong expression was in the 18 dpi group. In addition, the expression was positively correlated with the expression in placental ( = 0.99, < 0.01) and uterine tissues of mice in the 12 dpi group ( = 0.97, < 0.01) and in placental ( = 0.82, < 0.01) and uterine tissues of mice in the 18 dpi group ( = 0.81, < 0.01).

Conclusions: Following infection at early pregnancy, the and expression shows a remarkable rise at middle pregnancy and a reduction at late pregnancy in placental and uterine tissues of mice, which appears the same tendency with expression during the same time period, and expression positively correlates with expression. The dynamic expression of PD-1 and PD-L1 on the maternal-fetal interface of mice may be mutually mediated by IFN-γ induced by infection.