Placental Viral Infection Sensitizes to Endotoxin-Induced Pre-Term Labor: A Double Hit Hypothesis
Article first published online: 13 AUG 2010
© 2010 John Wiley & Sons A/S
American Journal of Reproductive Immunology
Volume 65, Issue 2, pages 110–117, February 2011
How to Cite
Cardenas, I., Mor, G., Aldo, P., Lang, S. M., Stabach, P., Sharp, A., Romero, R., Mazaki-Tovi, S., Gervasi, M. and Means, R. E. (2011), Placental Viral Infection Sensitizes to Endotoxin-Induced Pre-Term Labor: A Double Hit Hypothesis. American Journal of Reproductive Immunology, 65: 110–117. doi: 10.1111/j.1600-0897.2010.00908.x
- Issue published online: 6 JAN 2011
- Article first published online: 13 AUG 2010
- Submitted June 28, 2010; accepted July 2, 2010.
- Double hit hypothesis;
- toll-like receptors;
- viral infection
Citation Cardenas I, Mor G, Aldo P, Lang SM, Stabach P, Sharp A, Romero R, Mazaki-Tovi S, Gervasi MTeresa, Means RE. Placental viral infection sensitizes to endotoxin-induced pre-term labor: a double hit hypothesis. Am J Reprod Immunol 2011; 65: 110–117
Problem Among pregnant women, acquired viral infections with a concurrent bacterial infection is a detrimental factor associated to poor prognosis. We evaluate the effect of a viral infection that does not lead to pre-term labor on the response to low doses of lipopolysaccharide (LPS). Our objectives were (i) to characterize the effect of a viral infection concurrent with exposure to microbial products on pregnancy outcome and (ii) to characterize the placental and fetal immune responses to the viral sensitization to LPS.
Method C57B/6 wild-type mice were injected with murine gammaherpesvirus 68 (MHV68) at E8.5. Either PBS or LPS was injected i.p. at E15.5. Pregnancy outcome and cytokine/chemokine profile from implantation sites were analyzed by multiplex.
Results LPS treatment of MHV-68-infected animals induced pre-term delivery and fetal death in 100% of the mice. Pre-term labor was characterized by a upregulation of pro-inflammatory cytokines and chemokines in both placenta and decidua. Similar profiles were observed from MHV-68-infected human primary trophoblast and trophoblast cell lines in response to LPS.
Conclusion We describe for the first time that a sub-clinical viral infection in pregnant mice might sensitize to a bacterial infection leading to pre-term delivery. We propose the ‘Double Hit Hypothesis’ where the presence of a viral infection enhances the effect of bacterial products during pregnancy leading not only to pre-term labor but likely larger adverse outcomes.