Expression and secretion of antiviral factors by trophoblast cells following stimulation by the TLR-3 agonist, Poly(I : C)

Hum Reprod. 2006 Sep;21(9):2432-9. doi: 10.1093/humrep/del178. Epub 2006 Jun 3.

Abstract

Background: During pregnancy, the placenta may become exposed to micro-organisms, such as viruses, which may pose a substantial threat to the embryo/fetus well-being. Recent insight into the immunological capabilities of the trophoblast suggests that the placenta may function as an active barrier by recognizing and responding to pathogens through Toll-like receptors (TLRs).

Methods: The objective of this study was to determine whether the engagement of TLR-3 with viral dsRNA by first-trimester trophoblast could induce the production of factors necessary to generate an antiviral response. Therefore, trophoblast cells were exposed to the TLR-3 agonist, Poly(I : C).

Results: We report that following stimulation with Poly(I : C), first-trimester trophoblast cells produce interferon beta (IFNbeta) and secretory leukocyte protease inhibitor (SLPI), as well as the intracellular factors 2',5'-oligoadenylate synthetase (OAS), Myxovirus-resistance A (MxA) and apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3G (APOBEC3G). This response is TLR-3 specific because the TLR-4 ligand, lipopolysaccharide (LPS), had no effect on the production of these antimicrobial factors. Furthermore, we describe a positive feedback mechanism in which IFNbeta enhances the antiviral response by promoting the production of OAS, MxA and APOBEC3G.

Conclusions: These findings suggest that trophoblast cells are able to recognize and specifically respond to viral products in a highly regulated fashion and that the placenta may be pivotal in the control of viral infections at the maternal-fetal interface.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Antiviral Agents / pharmacology*
  • Apolipoproteins B / chemistry
  • Female
  • Humans
  • Ligands
  • Lipopolysaccharides / metabolism
  • Poly I-C / pharmacology*
  • Pregnancy
  • Pregnancy Trimester, First
  • RNA, Double-Stranded / chemistry
  • Reverse Transcriptase Polymerase Chain Reaction
  • Toll-Like Receptor 3 / agonists*
  • Trophoblasts / metabolism*

Substances

  • Antiviral Agents
  • Apolipoproteins B
  • Ligands
  • Lipopolysaccharides
  • RNA, Double-Stranded
  • Toll-Like Receptor 3
  • Poly I-C