Project 3: Decidual NK cell response to infection
For the longest time, decidual NK cells were considered low cytotoxic cells with unique capacities to secrete cytokine and growth factors to promote trophoblast invasion and placental development. Despite dNK high expression of cytolytic granules (perforin, granzyme B, and granulysin), their cytolytic responses to pathogen infected cells was not studied.
Dr. Tilburgs and colleagues demonstrated that dNK are able to kill virus (HCMV) infected decidual stromal cells but not HCMV-infected fetal trophoblasts, suggesting that viral infections are not well-controlled in the placenta.
Moreover, expression of the activating NK receptor KIR2DS1 on dNK and its interaction with HLA-C increased dNK degranulation and leads to enhanced immunity. This may explain how KIR2DS1 reduces risk for pregnancy complications as was shown by Hiby and Moffett et al., in genetic studies.
Other projects include the novel finding that dNK selectively transfer granulysin to kill bacteria inside trophoblasts without killing the trophoblasts and the unique differences found between decidual NK cells in early pregnancy and at term pregnancy. Key research questions are to determine whether separate populations of dNK responsible for placental development and immunity exist and how dysfunction of dNK contributes to pregnancy complications including maternal to fetal transmission of pathogens.
Collaborators:
Dr. Christian Karsten, University of Lübeck, Germany

Project 3: Decidual NK cell response to infection. Confocal image of decidual NK cell filled with the cytolytic granules perforin (red) and granulysin (green).