Inactivation of the MAPK signaling pathway by Listeria monocytogenes infection promotes trophoblast giant cell death.
Inactivation of the MAPK signaling pathway by Listeria monocytogenes infection promotes trophoblast giant cell death.
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DOI：
10.3389/fmicb.2015.01145
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发表时间：
2015
影响因子：
5.2
通讯作者：
Watarai M
中科院分区：
文献类型：
--
作者：
Hashino M;Tachibana M;Nishida T;Hara H;Tsuchiya K;Mitsuyama M;Watanabe K;Shimizu T;Watarai M
单核细胞增生李斯特菌具有很好的穿透胎盘屏障的能力，导致自然流产和胎儿感染。然而，导致感染相关流产的机制尚不完全清楚。在这项研究中，我们证明了单核增生乳杆菌感染滋养层巨细胞（TG）引起的MAPK家族蛋白的去磷酸化，导致了胎盘免疫细胞的感染性流产。在感染的TG细胞中观察到c-Jun、p38和ERK1/2的去磷酸化，导致细胞保护性血红素加氧酶(HO)-1的下调。阻断蛋白的去磷酸化，包括MAPK家族蛋白，抑制HO-1表达的下降。用MAPK抑制剂抑制细菌内化进入TG细胞。此外，toll样受体2参与MAPK家族蛋白的表达。在小鼠模型中，李斯特菌溶素o缺失突变体感染会破坏TG细胞中MAPK家族蛋白的去磷酸化，并且不会诱导感染性流产。这些结果表明，单核增生乳杆菌使MAPK通路失活可诱导TG细胞死亡并引起感染性流产。
Listeria monocytogenes has a well-characterized ability to cross the placental barrier, resulting in spontaneous abortion and fetal infections. However, the mechanisms resulting in infection-associated abortion are not fully understood. In this study, we demonstrate that the dephosphorylation of MAPK family proteins caused by L. monocytogenes infection of trophoblast giant (TG) cells, which are placental immune cells, contributes to infectious abortion. Dephosphorylation of c-Jun, p38, and ERK1/2 was observed in infected TG cells, causing the downregulation of cytoprotective heme oxygenase (HO)-1. Blocking the dephosphorylation of proteins, including MAPK family proteins, inhibited the decrease in HO-1 expression. Treatment with MAPK inhibitors inhibited bacterial internalization into TG cells. Moreover, Toll-like receptor 2 involved in the expression of MAPK family proteins. Infection with a listeriolysin O-deleted mutant impaired dephosphorylation of MAPK family proteins in TG cells and did not induce infectious abortion in a mouse model. These results suggest that inactivation of the MAPK pathway by L. monocytogenes induces TG cell death and causes infectious abortion.