中文摘要：
母体免疫激活（MIA）会导致子代神经发育缺陷，但其产前机制仍不清楚。在本研究中，我们利用产前暴露于弓形虫可溶性速殖子抗原（STAg）诱导的小鼠MIA模型，发现以厚壁菌门和放线菌门增加为特征的母体肠道菌群失调，会驱动子代行为缺陷。这种菌群失调破坏肠道屏障完整性，并诱导代谢与炎症失调，表现为M1型巨噬细胞和IL-6升高，同时甘油磷脂代谢物1-油酰-2-肉豆蔻酰-sn-甘油-3-磷酸胆碱（OMPC）显著蓄积，进而导致胎盘炎症、胎儿神经炎症和子代行为异常等不良结局。机制上，OMPC与巨噬细胞上的Tnfrsf25结合，激活JAK1/STAT3/IL-6信号通路。关键在于，母体补充鼠李糖乳杆菌GG（LGG）可恢复肠道免疫稳态，减轻胎盘炎症和胎儿神经炎症，并挽救子代行为损伤。总之，我们的研究将OMPC/JAK1/STAT3/IL-6信号通路界定为MIA中的致病枢纽，并提名LGG作为一种产前预防策略，以减轻神经发育障碍。
英文摘要：
Maternal immune activation (MIA) contributes to neurodevelopmental deficits in offspring, yet the prenatal mechanisms remain elusive. Here, using a mouse MIA model induced by prenatal exposure to Toxoplasma gondii soluble tachyzoite antigen (STAg), we reveal that maternal gut dysbiosis, characterized by increased Firmicutes and Actinobacteria, drives offspring behavioral deficits. This dysbiosis disrupts intestinal barrier integrity and induces metabolic and inflammatory dysregulation, characterized by elevated M1 macrophages and IL-6, alongside a pronounced accumulation of the glycerophospholipid metabolite 1-oleoyl-2-myristoyl-sn-glycero-3-phosphocholine (OMPC), resulting in adverse outcomes including placental inflammation, fetal neuroinflammation, and behavioral abnormalities in offspring. Mechanistically, OMPC binds to Tnfrsf25 on macrophages, activating JAK1/STAT3/IL-6 signaling. Crucially, maternal probiotic supplementation with Lactobacillus rhamnosus GG (LGG) restores gut-immune homeostasis, attenuates placental inflammation and fetal neuroinflammation, and rescues offspring behavioral impairments. Collectively, our findings define OMPC/JAK1/STAT3/IL-6 signaling as a pathogenic hub in MIA and nominate LGG as a prenatal prophylactic strategy to mitigate neurodevelopmental disorders.
论文信息：
论文题目：Maternal immune activation perturbs intestinal niche through microbial glycerophospholipids and drives offspring behavioral abnormalities
期刊名称：Cell Reports
时间期卷：Volume 45, Issue4, 117211
DOI: 10.1016/j.celrep.2026.117211
产品信息：
货号：CP-005-005
规格：5ml+5ml
品牌：Liposoma
产地：荷兰
名称：Clodronate Liposomes&Control Liposomes
办事处：靶点科技
Clodronate Liposomes氯膦酸盐脂质体清除孕鼠模型巨噬细胞，荷兰Liposoma巨噬细胞清除剂ClodronateLiposomes见刊于Cell Reports：母体免疫激活通过微生物甘油磷脂扰乱肠道生态位，并驱动子代行为异常。
Liposoma巨噬细胞清除剂Clodronate Liposomes氯膦酸二钠脂质体清除巨噬细胞的材料和方法：
In vivo macrophage depletion
To further elucidate the impact of macrophages on OMPC-driven IL-6 production, we effectively depleted macrophages in pregnant dams through i.p. injection of clodronate liposomes (Clo-lip) and control liposomes (Con-lip) (Figure S8J). Flow cytometry and immunofluorescence analyses confirmed the significant reduction of macrophages in both the maternal peritoneal cavity and intestine in OMPC-gavaged dams treated with Clo-lip (Figures S8K and S8L). RT-qPCR analysis demonstrated Il6 mRNA expression levels significantly downregulated in the maternal colon and small intestine of the OMPC-gavaged dams treated with Clo-lip dams compared with the OMPC-gavaged dams treated with Con-lip (Figure S8M). Furthermore, immunofluorescence analysis confirmed a significant decrease in IL-6 protein expression in the maternal intestine of OMPC-gavaged dams treated with Clo-lip dams (Figure S8N). Altogether, the macrophages are essential for OMPC-driven IL-6 production in vivo.
巨噬细胞清除材料和方法文献截图：
