Activation of TLR3 in the trophoblast is associated with preterm delivery.
OBJECTIVE
Toll-like receptors (TLRs) recognize conserved sequences on the surface of pathogens and trigger effector cell functions. Previously, we described the expression of TLR3 by human trophoblast and their ability to respond to (Poly[I:C]). Here we evaluate the effect of Poly[I:C] on mouse pregnancy and characterize the local and systemic response.


METHODS
C57B/6 wild type (wt) and TLR3 knockout (TLR3KO) mice were treated with Poly[I:C] at 16.5 dpc and pregnancy outcome recorded. Morphologic changes, cytokines and chemokines levels in blood and utero-placental tissue were determined. NF-kappaB pathway was evaluated in vivo and in vitro.


RESULTS
Poly[I:C] in C57B/6 wt mice caused preterm delivery within 24 hr (4.5 mg/kg). No effect was observed in TLR3KO mice. In addition, we observed local (placenta) and systemic (serum) response characterized by increased production of proinflammatory cytokines and chemokines. The NF-kappaB pathway was activated by Poly[I:C] in human and mice trophoblast cells.


CONCLUSIONS
We report that Poly[I:C] induces preterm delivery via TLR3-dependent manner. Furthermore, we demonstrate that the trophoblast is able to recognize Poly[I:C] through TLR3 and respond to viral infection, modulating the immune system at the feto-maternal interface.
Koga
Kaori
K
Department of Obstetrics and Gynecology and Reproductive Science, Yale University School of Medicine, New Haven, CT, USA.
Cardenas
Ingrid
I
Aldo
Paulomi
P
Abrahams
Vikki M
VM
Peng
Bing
B
Fill
Sara
S
Romero
Roberto
R
Mor
Gil
G
D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000097:blood / Q000187:drug effects; D005260:Female; D006801:Humans; D007369:Interferon Inducers / Q000008:administration & dosage / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism; D010920:Placenta / Q000276:immunology / Q000821:virology; D011070:Poly I-C / Q000276:immunology; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000821:virology*; D047928:Premature Birth / Q000276:immunology* / Q000473:pathology / Q000821:virology; D051196:Toll-Like Receptor 3 / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D014327:Trophoblasts / Q000276:immunology* / Q000821:virology; D014777:Virus Diseases / Q000150:complications*
D016207:Cytokines; D007369:Interferon Inducers; D016328:NF-kappa B; C519703:TLR3 protein, mouse; D051196:Toll-Like Receptor 3; D011070:Poly I-C