PlGF enhances TLR-dependent inflammatory responses in human mononuclear phagocytes

Area of Science:

• Immunology
• Obstetrics
• Molecular Biology

Background:

• Placental growth factor (PlGF) levels are highest in the third trimester, a period of increased susceptibility to viral infections.
• Toll-like receptors (TLRs) are crucial in the immune response to pathogens.

Purpose of the Study:

• To investigate the role of PlGF in modulating inflammatory responses to TLR activation.
• To determine if PlGF contributes to exaggerated inflammation during pregnancy.

Main Methods:

• Primary human adult and cord blood monocytes (CD14+ cells) were cultured with TLR ligands and PlGF.
• Analyzed Tumor Necrosis Factor (TNF) mRNA and protein production.
• Assessed IkappaB kinase (IKK) phosphorylation and the effect of IKK inhibition.

Main Results:

• PlGF significantly increased TNF production in monocytes activated by TLR-7/8 agonists.
• PlGF prolonged TNF production and induced other inflammatory cytokines independently of TNF.
• PlGF enhanced IKK phosphorylation, a key step in TLR signaling, which was blocked by IKK inhibitors.

Conclusions:

• PlGF potentiates TLR signaling upstream of IKK.
• PlGF contributes to an exaggerated pro-inflammatory state in maternal and fetal immune cells upon TLR activation.
• This mechanism may underlie increased pregnancy morbidity associated with viral infections.