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.
Highlights
Human listeriosis is a food-borne disease resulting from the ingestion of contaminated food, such as dairy products, vegetables, raw seafood, poultry, and processed meat (Hernandez-Milian and Payeras-Cifre, 2014)
Because the mitogen-activated protein kinase (MAPK) pathway is involved in the infection of host cells by bacterial pathogens (Krachler et al, 2011), the phosphorylation of c-Jun, p38, and ERK1/2 in trophoblast giant (TG) cells after L. monocytogenes infection was analyzed by immunoblotting
Phosphorylation of c-Jun, p38, and ERK1/2 was observed in uninfected control TG cells, whereas dephosphorylation of these proteins was observed in infected TG cells (Figures 1A,B)
Summary
Human listeriosis is a food-borne disease resulting from the ingestion of contaminated food, such as dairy products, vegetables, raw seafood, poultry, and processed meat (Hernandez-Milian and Payeras-Cifre, 2014). Infection of B. abortus induced a transient increase in interferon-γ (IFN-γ) levels in pregnant mice This transient IFN-γ production leads to infectious abortion, and depletion of IFN-γ by neutralization inhibits infectious abortion (Kim et al, 2005). These reports of B. abortus infection imply that bacterial internalization and intracellular replication in TG cells are both key aspects in abortion and that TG cells are closely associated with the evasion of maternal immune rejection
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