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Am J Reprod Immunol. 2016 Apr;75(4):451-60. doi: 10.1111/aji.12501. Epub 2016 Feb 19.

Type I Interferon Regulates the Placental Inflammatory Response to Bacteria and is Targeted by Virus: Mechanism of Polymicrobial Infection-Induced Preterm Birth.

Author information

1
Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA.
2
Department of OB/GYN, College of Human Medicine, Michigan State University, Grand Rapids, MI, USA.
3
Department of OB/GYN, Institute of Women's Life Medical Science, Yonsei University College of Medicine, Seoul, Korea.
4
Department of Pediatrics, Yale School of Medicine, New Haven, CT, USA.
5
Perinatology Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS, Detroit, MI, USA.

Abstract

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

PMID:
26892235
PMCID:
PMC5599852
DOI:
10.1111/aji.12501
[Indexed for MEDLINE]
Free PMC Article

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