TLR9 provokes inflammation in response to fetal DNA: mechanism for fetal loss in preterm birth and preeclampsia

UMMS Affiliation

Department of Medicine, Division of Infectious Diseases and Immunology

Publication Date


Document Type



Adult; Animals; Cell Line, Tumor; Cells, Cultured; DNA; Female; Fetal Death; Humans; Inflammation Mediators; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Middle Aged; Pre-Eclampsia; Pregnancy; Premature Birth; Toll-Like Receptor 9


Immunology and Infectious Disease | Maternal and Child Health | Obstetrics and Gynecology


Preterm birth, the major cause of neonatal mortality in developed countries, is associated with intrauterine infections and inflammation, although the exact mechanisms underlying this event are unclear. In this study, we show that circulating fetal DNA, which is elevated in pregnancies complicated by preterm labor or preeclampsia, triggers an inflammatory reaction that results in spontaneous preterm birth. Fetal DNA activates NF-kappaB, shown by IkappaBalpha degradation in human PBMCs resulting in production of proinflammatory IL-6. We show that fetal resorption and preterm birth are rapidly induced in mice after i.p. injection of CpG or fetal DNA (300 mug/dam) on gestational day 10-14. In contrast, TLR9(-/-) mice were protected from these effects. Furthermore, this effect was blocked by oral administration of the TLR9 inhibitor chloroquine. Our data therefore provide a novel mechanism for preterm birth and preeclampsia, highlighting TLR9 as a potential therapeutic target for these common disorders of pregnancy.

DOI of Published Version



J Immunol. 2012 Jun 1;188(11):5706-12. doi: 10.4049/jimmunol.1103454. Link to article on publisher's site

Journal/Book/Conference Title

Journal of immunology (Baltimore, Md. : 1950)

Related Resources

Link to Article in PubMed

PubMed ID