Anna Bakardjiev, MD
Research in our laboratory focuses on understanding the mechanisms that lead to infection of the placenta. The placenta is an extraordinary organ, differing from others because it has to protect the fetus from rejection by the maternal immune system and from pathogens. Thus, the placenta has to provide an environment of immune tolerance and host defense at the same time. How this is achieved is largely unknown. Out of the myriad of microbes only a few are known to infect the placenta, which suggests that the placenta has strong defensemechanisms. The known placental pathogens include a few viruses, bacteria, and protists. Interestingly, these disparate organisms have one thing in common: they have intracellular life cycles. Among these is the bacterium Listeria monocytogenes and the protist Toxoplasma gondii. Our lab has investigated both of these pathogens. However, we are predominantly using L. monocytogenes, a well-characterized intracellular pathogen that is highly amenable to experimental analysis and thus provides us with valuable molecular tools. A major limitation to our understanding of placental and fetal infections has been the lack of an animal model for human disease. The mouse is not a good model. Therefore, we developed a pregnant guinea pig model of listeriosis that replicates human disease, and we have used it to identify listerial virulence determinants that are important for bacterial growth in the placenta in vivo. In order to perform in vitro experiments in a physiologically highly relevantmodel system we are using primary human placental organ and cell culture models. With these tools in hand we are attempting to improve our understanding of the molecular and cellular mechanisms of host-pathogen interactions in the placenta, which will shed insights into mechanisms of prematurity and congenital infections.