Type I interferon regulates the placental inflammatory response to bacteria and is targeted by virus: mechanism of polymicrobial infection‐induced preterm birth
K Racicot, JY Kwon, P Aldo, V Abrahams… - American journal of …, 2016 - Wiley Online Library
American journal of reproductive immunology, 2016•Wiley Online Library
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, C57 BL/6,
and interferon (IFN) receptor knockout animals were used to determine IFN function. Illumina …
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, C57 BL/6,
and interferon (IFN) receptor knockout animals were used to determine IFN function. Illumina …
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.
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