Tachibana Masato, Hashino Masanori, Watanabe Kenta, Shimizu Takashi, Watarai Masahisa
The United Graduate School of Veterinary Science, Yamaguchi University, Yamaguchi, Japan.
Sci Rep. 2015 Feb 3;5:8195. doi: 10.1038/srep08195.
Listeria monocytogenes is well known for having the ability to cross the placental barrier, leading to fetal infections and abortion. However, the mechanisms leading to infectious abortion are poorly understood. In this study, we demonstrate that interferon γ-induced GTPase (IGTP) contributes to the invasion of L. monocytogenes into trophoblast giant (TG) cells, which are placental immune cells. Knockdown of IGTP in TG cells decreased the relative efficiencies of L. monocytogenes invasion. Moreover, IGTP accumulated around infected L. monocytogenes in TG cells. Treatment of TG cells with phosphatidylinositol 3-kinase (PI3K)/Akt inhibitors also reduced bacterial invasion. PI3K/Akt inhibitor or IGTP knockdown reduced the amount of phosphorylated Akt. Monosialotetrahexosylganglioside (GM1) gangliosides, lipid raft markers, accumulated in the membrane of L. monocytogenes-containing vacuoles in TG cells. Furthermore, treatment with a lipid raft inhibitor reduced bacterial invasion. These results suggest that IGTP-induced activation of the PI3K/Akt signaling pathway promotes bacterial invasion into TG cells.
单核细胞增生李斯特菌以能够穿越胎盘屏障、导致胎儿感染和流产而闻名。然而，导致感染性流产的机制尚不清楚。在本研究中，我们证明干扰素γ诱导的GTP酶（IGTP）有助于单核细胞增生李斯特菌侵入滋养层巨细胞（TG细胞），TG细胞是胎盘免疫细胞。在TG细胞中敲低IGTP会降低单核细胞增生李斯特菌的相对入侵效率。此外，IGTP在TG细胞中感染的单核细胞增生李斯特菌周围聚集。用磷脂酰肌醇3激酶（PI3K）/Akt抑制剂处理TG细胞也会减少细菌入侵。PI3K/Akt抑制剂或IGTP敲低会减少磷酸化Akt的量。单唾液酸四己糖神经节苷脂（GM1）神经节苷脂是脂筏标志物，在TG细胞中含单核细胞增生李斯特菌的液泡膜中积累。此外，用脂筏抑制剂处理会减少细菌入侵。这些结果表明，IGTP诱导的PI3K/Akt信号通路激活促进细菌侵入TG细胞。
