Role of Toll-like receptors in trophoblast immune regulation
Toll-like Receptors (TLRs) mediate trophoblast recognition of the uterine microenvironment that under normal conditions contain commensal microbes and stress proteins, and respond to it by recruiting a large number of immune cells, such as macrophages, Natural killer (NK) cells and regulatory T cells (Treg), all found in the decidua. The appropriate communication between all these cellular components at the maternal-fetal interface is crucial for successful reproduction. TLRs expressed by the trophoblast function as sensors which induce the production of cytokines/chemokines that will in turn regulate immune cell distribution and function at the maternal-fetal interface. However, if the function of TLRs is left unchecked, the maternal-fetal interface may become overwhelmed by immune activation. Therefore, TLR function and signaling must be tightly regulated in order to prevent pathological conditions.
The studies of Project I evaluate the supportive regulatory interactions between first trimester trophoblasts and the maternal immune system. They also investigate the role of Toll-like Receptors (TLR) in these processes. The objectives of Project I are to:
- Understand TLR function in first trimester trophoblast cells
- Determine the effects of trophoblast TLR activation on maternal immune cells
- Characterize regulatory mechanisms controlling TLR expression and function at the maternal-fetal interface
- Evaluate the role of TLRs in pregnancy outcome
Aim I: Determine cytokine profile in first trimester trophoblast cells following TLR ligation
Aim II: Characterize the effect of trophoblast TLR activation on immune cell recruitment and function.
Aim III: Study the regulation of TLR expression and function in trophoblast cells.
Aim IV: In vivo studies for the characerization of TLR function in pregnancy.