Hormonal modulation of the Type I Interferon response during pregnancy: implications formaternal health and disease

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Pregnant mammals have to mount immunological tolerance towards the fetus. Adaptation of the maternal immune system to pregnancy is achieved by the cross-talk between maternal hormones, immune cells and semiallogenic fetal/placental cells. However, this feto-maternal immune crosstalk also has significant consequences for maternal health, including amelioration of multiple sclerosis (MS), but also increased susceptibility to some viral infections. Type I IFNs play a central role in the regulation of both the immune response to viral infections and autoimmune diseases. However, little is known about the consequences of pregnancy and pregnancy-related sex hormones for the Type I IFN pathway and its regulation. In this project, we will test the hypothesis that pregnancy-related hormones lead to changes in innate immune pathways critical for pathogen recognition and inflammation. These pregnancy-induced changes of the Type I IFN pathway might result in modulated susceptibility to viral infections, but also a reduced severity of some autoimmune diseases. A better understanding of the interplay between pregnancy, sex hormones and Type I IFNs will be critical to guide novel therapeutic interventions to ameliorate the health of pregnant women.