TY - JOUR
T1 - Inactivation of the MAPK signaling pathway by Listeria monocytogenes infection promotes trophoblast giant cell death
AU - Hashino, Masanori
AU - Tachibana, Masato
AU - Nishida, Takashi
AU - Hara, Hideki
AU - Tsuchiya, Kohsuke
AU - Mitsuyama, Masao
AU - Watanabe, Kenta
AU - Shimizu, Takashi
AU - Watarai, Masahisa
N1 - Publisher Copyright:
© 2015 Hashino, Tachibana, Nishida, Hara, Tsuchiya, Mitsuyama, Watanabe, Shimizu and Watarai.
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
KW - Abortion
KW - Infection
KW - Listeria monocytogenes
KW - MAPK
KW - Placenta
KW - Trophoblast
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U2 - 10.3389/fmicb.2015.01145
DO - 10.3389/fmicb.2015.01145
M3 - Article
AN - SCOPUS:84946819085
VL - 6
JO - Frontiers in Microbiology
JF - Frontiers in Microbiology
SN - 1664-302X
IS - OCT
M1 - 1145
ER -