Placental viral infection sensitizes to endotoxin-induced pre-term labor: a double hit hypothesis.

Abstract

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.

• Authors: Ingrid Cardenas, Gil Mor, Paulomi Aldo, Sabine M Lang, Paul Stabach, Andrew Sharp, Roberto Romero, Shali Mazaki-Tovi, MariaTeresa Gervasi, Robert E Means
• Journal: American journal of reproductive immunology (New York, N.Y. : 1989) (Am J Reprod Immunol) Vol. 65 Issue 2 Pg. 110-7 (Feb 2011) ISSN: 1600-0897 [Electronic] Denmark
• PMID: 20712808 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural)
• Copyright: © 2010 John Wiley & Sons A/S.

Chemical References

• Endotoxins
• Lipopolysaccharides

Topics

• Animals
• Bacterial Infections (immunology, microbiology)
• Endotoxins (pharmacology)
• Female
• Fetal Death
• Herpesviridae Infections (virology)
• Humans
• Labor, Induced
• Lipopolysaccharides (pharmacology)
• Mice
• Mice, Inbred C57BL
• NIH 3T3 Cells
• Obstetric Labor, Premature (etiology)
• Placenta (drug effects, virology)
• Placenta Diseases (immunology, microbiology, virology)
• Pregnancy
• Rhadinovirus (pathogenicity)
• Tumor Virus Infections (virology)