Staphylococcus aureus is an infectious pathogen that is relatively common, but that can cause severe disease in pregnant women and their fetus. We previously demonstrated that exposing pregnant rats to staphylococcal enterotoxin B (SEB) altered splenic CD4/CD8 T cell frequencies in their offspring. Whether prenatal SEB exposure impacts Tregs in these offspring, however, remains to be determined. As such, in this study, we intravenously injected pregnant rats with 15 μg of SEB on gestational day 16. Splenic tissue was then harvested from 1-, 3-, and 5-day-old neonatal rats and analyzed via flow cytometry to assess Treg numbers. In addition, FoxP3 expression levels were assessed via qPCR and western blotting, while FoxP3 methylation status was evaluated via methyl-DNA immunoprecipitation qPCR. Immunosuppression assays were additionally used to gauge Treg suppressive functionality. We found that exposing pregnant rats to SEB resulted in a significant increase in Treg numbers, FoxP3 expression, and Treg suppressive capacity in the spleens of both neonatal and adult offspring. In addition, total T cell, CD4⁺T cell, and non-Treg CD4⁺ T cell numbers were elevated in the spleens of offspring following prenatal SEB exposure. We additionally determined that SEB exposure resulted in a significant reduction in FoxP3 DNA methylation. Together, our results indicate that prenatal SEB exposure can markedly enhance offspring splenic Treg numbers and functionality at least in part by decreasing FoxP3 methylation.

金黄色葡萄球菌是一种相对常见的传染性病原体，但可引起孕妇及其胎儿的严重疾病。我们之前证明，将怀孕的大鼠暴露于葡萄球菌肠毒素 B (SEB) 会改变其后代的脾脏 CD4/CD8 T 细胞频率。然而，产前 SEB 暴露是否会影响这些后代的 Tregs 仍有待确定。因此，在本研究中，我们在妊娠第 16 天给怀孕大鼠静脉注射 15 μg SEB。然后从 1、3 和 5 日龄新生大鼠中采集脾组织，并通过流式细胞术进行分析以评估 Treg数字。此外，通过 qPCR 和蛋白质印迹评估 FoxP3 表达水平，同时通过甲基 DNA 免疫沉淀 qPCR 评估 FoxP3 甲基化状态。另外还使用免疫抑制测定来测量 Treg 抑制功能。我们发现，将怀孕大鼠暴露于 SEB 会导致新生和成年后代脾脏中 Treg 数量、FoxP3 表达和 Treg 抑制能力显着增加。此外，产前 SEB 暴露后，子代脾脏中的总 T 细胞、CD4 ⁺ T 细胞和非 Treg CD4 ⁺ T 细胞数量升高。我们还确定 SEB 暴露导致 FoxP3 DNA 甲基化显着减少。总之，我们的结果表明，产前 SEB 暴露可以显着增强后代脾 Treg 数量和功能，至少部分是通过降低 FoxP3 甲基化来实现的。