Viral single stranded RNA induces a trophoblast pro-inflammatory and antiviral response in a TLR8-dependent and -independent manner

Julie A. Potter, Manish Garg, Sylvie Girard, Vikki M. Abrahams

Research output: Contribution to journalArticlepeer-review


Interest is growing in the role of viral infections and their association with adverse pregnancy outcomes. The trophoblast is permissive to viruses, but little is known about their impact on the placenta. We previously established that viral single stranded RNA (ssRNA), a Toll-like receptor 8 (TLR8) agonist, induces a restricted trophoblast pro-inflammatory cytokine/chemokine response by upregulating the secretion of interleukin (IL)-6 and IL-8. In parallel, the type I interferon, IFNbeta, is produced and acts back on the cell in an autocrine/paracrine manner to trigger caspase-3-dependent apoptosis. In this study, we sought to extend these findings by determining the mechanisms involved, examining whether viral ssRNA could induce a trophoblast antiviral response, and evaluating the influence of viral ssRNA on pregnancy outcome using a mouse model. Viral ssRNA induced human first-trimester trophoblast inflammation, type I interferon production, an antiviral response, and apoptosis in both a TLR8/MyD88-dependent and -independent manner. Furthermore, administration of viral ssRNA to pregnant mice induced placental caspase-3 activation, a pro-inflammatory cytokine/chemokine, type I interferon, and antiviral response as well as immune cell infiltration. Thus, ssRNA viral infections may compromise pregnancy by altering placental trophoblast survival and function through both TLR8 and non-TLR8 signaling pathways, leading to immune changes at the maternal-fetal interface.

Original languageEnglish (US)
Article number17
JournalBiology of Reproduction
Issue number1
StatePublished - Jan 1 2015


  • Antiviral
  • Apoptosis
  • Cytokines
  • Inflammation
  • Pregnancy
  • Reproductive immunology
  • Toll-like receptors
  • Trophoblast
  • Viral ssRNA

ASJC Scopus subject areas

  • Reproductive Medicine
  • Cell Biology


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