title: Inactivation of the MAPK signaling pathway by Listeria monocytogenes infection promotes trophoblast giant cell death.
abstract: 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.
authors.affiliation: The United Graduate School of Veterinary Science, Yamaguchi University, Yoshida Campus Yamaguchi, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Hashino
authors.affiliation: The United Graduate School of Veterinary Science, Yamaguchi University, Yoshida Campus Yamaguchi, Japan ; Division of Biomedical Food Research, National Institute of Health Sciences Tokyo, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Tachibana
authors.affiliation: The United Graduate School of Veterinary Science, Yamaguchi University, Yoshida Campus Yamaguchi, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Nishida
authors.affiliation: Department of Microbiology, Graduate School of Medicine, Kyoto University Kyoto, Japan ; Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School Ann Arbor, MI, USA.
authors.forename: Hideki
authors.initials: H
authors.lastname: Hara
authors.affiliation: Department of Microbiology, Graduate School of Medicine, Kyoto University Kyoto, Japan ; Division of Immunology and Molecular Biology, Cancer Research Institute, Kanazawa University Kanazawa, Japan.
authors.forename: Kohsuke
authors.initials: K
authors.lastname: Tsuchiya
authors.affiliation: Department of Microbiology, Graduate School of Medicine, Kyoto University Kyoto, Japan ; Graduate School of Advanced Integrated Studies in Human Survivability, Kyoto University Kyoto, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Mitsuyama
authors.affiliation: The United Graduate School of Veterinary Science, Yamaguchi University, Yoshida Campus Yamaguchi, Japan ; Laboratory of Veterinary Public Health, Joint Faculty of Veterinary Medicine, Yamaguchi University at Yamaguchi Yamaguchi, Japan.
authors.forename: Kenta
authors.initials: K
authors.lastname: Watanabe
authors.affiliation: The United Graduate School of Veterinary Science, Yamaguchi University, Yoshida Campus Yamaguchi, Japan ; Laboratory of Veterinary Public Health, Joint Faculty of Veterinary Medicine, Yamaguchi University at Yamaguchi Yamaguchi, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Shimizu
authors.affiliation: The United Graduate School of Veterinary Science, Yamaguchi University, Yoshida Campus Yamaguchi, Japan ; Laboratory of Veterinary Public Health, Joint Faculty of Veterinary Medicine, Yamaguchi University at Yamaguchi Yamaguchi, Japan.
authors.forename: Masahisa
authors.initials: M
authors.lastname: Watarai
keywords: Listeria monocytogenes; MAPK; abortion; infection; placenta; trophoblast