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Abstract
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.
Highlights
Listeria monocytogenes is well known for having the ability to cross the placental barrier, leading to fetal infections and abortion
In Brucella infection, we found that there was a higher degree of bacterial colonization in the placenta than in other organs, that there were many bacteria in trophoblast giant (TG) cells in the placenta and that abortion was not induced in an intracellular replication-defective mutant[11]
We demonstrated that IFN-c promotes bacterial invasion into TG cells[27,28]
Summary
Listeria monocytogenes is well known for having the ability to cross the placental barrier, leading to fetal infections and abortion. We demonstrate that interferon c-induced GTPase (IGTP) contributes to the invasion of L. monocytogenes into trophoblast giant (TG) cells, which are placental immune cells. This transient IFN-c production contributes to infectious abortion, and its neutralization serves to prevent abortion[11] These studies of Brucella infection suggest that bacterial infection of TG cells plays a key role in causing abortion and that TG cells are closely linked to the avoidance of maternal immune rejection. IFN-c-induced GTPase (IGTP), known as Irgm[3], belongs to a family of 47 kDa IFN-c-responsive GTPases (IRG) These family proteins are known to play critical roles in mediating specific resistance to intracellular pathogens including protozoa, bacteria and viruses[18,19,20]. IGTP has been found to be essential for host resistance to acute infections by the protozoans Toxoplasma gondii[23] and Leishmania major[22], but its antimicrobial mechanism is still not clear
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