| First Author | Racicot K | Year | 2016 |
| Journal | Am J Reprod Immunol | Volume | 75 |
| Issue | 4 | Pages | 451-60 |
| PubMed ID | 26892235 | Mgi Jnum | J:350895 |
| Mgi Id | MGI:7664225 | Doi | 10.1111/aji.12501 |
| Citation | Racicot K, et al. (2016) Type I Interferon Regulates the Placental Inflammatory Response to Bacteria and is Targeted by Virus: Mechanism of Polymicrobial Infection-Induced Preterm Birth. Am J Reprod Immunol 75(4):451-60 |
| abstractText | 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-beta 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-beta pathway resulted in a significant increase in inflammatory cytokines such as IL-1B in response to LPS. Twist was positively correlated with IFN-beta 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-beta was identified as a key modulator of placental inflammation and, importantly, is commonly affected by viruses. We propose dysregulation of IFN-beta is a major determinant for preterm birth associated with polymicrobial infection. |
