Expression and secretion of antiviral factors by trophoblast cells following stimulation by the TLR-3 agonist, Poly(I : C).
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.
Abrahams
Vikki M
VM
Department of Obstetrics, Gynecology & Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520, USA.
Schaefer
Todd M
TM
Fahey
John V
JV
Visintin
Irene
I
Wright
Jacqueline A
JA
Aldo
Paulomi B
PB
Romero
Roberto
R
Wira
Charles R
CR
Mor
Gil
G
D000998:Antiviral Agents / Q000494:pharmacology*; D001055:Apolipoproteins B / Q000737:chemistry; D005260:Female; D006801:Humans; D008024:Ligands; D008070:Lipopolysaccharides / Q000378:metabolism; D011070:Poly I-C / Q000494:pharmacology*; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D012330:RNA, Double-Stranded / Q000737:chemistry; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051196:Toll-Like Receptor 3 / Q000819:agonists*; D014327:Trophoblasts / Q000378:metabolism*
D000998:Antiviral Agents; D001055:Apolipoproteins B; D008024:Ligands; D008070:Lipopolysaccharides; D012330:RNA, Double-Stranded; D051196:Toll-Like Receptor 3; D011070:Poly I-C