Problem: Preterm birth (PTB) affects approximately 12% of pregnancies and at least 50% of cases have no known risk factors. We hypothesize that subclinical viral infections of the placenta are a factor sensitizing women to intrauterine bacterial infection. Specifically, we propose that viral-induced placental IFN-β inhibition results in a robust inflammatory response to low concentrations of bacteria.
Methods: Human trophoblast SW.71, C57BL/6, and interferon (IFN) receptor knockout animals were used to determine IFN function. Illumina and Bio-Rad microarrays identified pathways.
Results: Inhibiting the IFN-β pathway resulted in a significant increase in inflammatory cytokines such as IL-1B in response to LPS. Twist was positively correlated with IFN-β expression and STAT3 phosphorylation and overexpressing Twist reduced IL-1B. Treating IFNAR-/- mice with low-dose LPS at E15.5 caused preterm birth.
Conclusion: IFN-β was identified as a key modulator of placental inflammation and, importantly, is commonly affected by viruses. We propose dysregulation of IFN-β is a major determinant for preterm birth associated with polymicrobial infection.
Keywords: Bacteria; infection; interferon; polymicrobial; pregnancy; trophoblast; virus.
© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.