Blogger: Guro Stødle and Line Tangerås
PhD students, CEMIR
In the human body, infections (caused by bacteria or virus) and tissue injury may set off an inflammatory response, in which immune cells, blood vessels, proteins and other mediators work together to eliminate the threat and repair the damage.
Pregnancy is a delicate setting where the mother and fetus must adapt properly to each other to coexist, and an inflammatory response can disturb this delicate balance and cause complications. This is seen in preeclampsia, a potentially severe inflammatory pregnancy disorder threatening both the mother and fetus.
In preeclampsia, inflammation in the placenta contributes to poor placental development, later leading to systemic inflammation in the mother, manifesting as high blood pressure and protein in the mother’s urine.
Inflammatory responses to injury or infection are directed by Toll-like receptors (TLRs). They are central to the body´s danger response machinery and initiate inflammation by recruiting all cells needed to repair the injury. The TLR expression of a cell defines its potential to respond to danger and take part in inflammation.
Fetal-derived trophoblasts are the main cell type of the placenta and initial reports indicate that these cells may express TLRs. To investigate a role for trophoblasts in placental inflammation, we performed a study in which we aimed to determine whether trophoblasts of early pregnancy expressed the ten TLRs and whether these receptors were responsive to danger signals. In this study, first trimester placenta tissue samples were collected at the Department of Gynecology and Obstetrics at St. Olavs Hospital and laboratory experiments were performed at the Centre of Molecular Inflammation Research (CEMIR) at NTNU. In December 2014 the results were published in Journal of Reproductive Immunology.
We discovered that trophoblasts isolated from first trimester placentas showed a broad TLR expression. Functional responses to danger signals were detected for six of the TLRs, and the activation led to production of pro-inflammatory cytokines. This clearly indicates a role for fetal trophoblasts in danger response and inflammation in the placenta, and that trophoblast TLRs may play an important role in inflammatory diseases during pregnancy, such as preeclampsia.
To understand how inflammatory responses can contribute to the development of preeclampsia, we will continue this work by comparing specific danger responses in samples (blood samples and placentas) from healthy pregnancies with samples from women who developed preeclampsia.
Read the article “Functional Toll-like receptors in primary first-trimester trophoblasts“.