Role of Hofbauer cells in prenatal inflammation at the maternal-fetal interface

PROJECT SUMMARY/ABSTRACT Prenatal inflammation is observed in pregnancy complications, especially those complicated with preterm birth (PTB). Prenatal inflammation is a major cause of neonatal mortality and morbidity with significant impacts on neurodevelopment as well as lung and immune system development. PTB affects 10-12% of births in the United States. The cellular process behind the subsequent altered placental inflammation is not fully understood, complicating attempts to treat or prevent it. Thus, the objective of this grant is to investigate the mechanisms through which placental resident macrophages, namely Hofbauer cells, are involved in the placental impact of prenatal inflammation. Hofbauer cells are the predominant immune cell type within the placenta; these macrophages are known to release pro-inflammatory cytokines when stimulated. The central hypothesis that the pro-inflammatory profile at the maternal-fetal interface with prenatal inflammation is primarily driven by Hofbauer cells will be addressed in two specific aims. First, the Hofbauer cell inflammatory profile in physiological birth (Term) vs. pathological pregnancies (PTB) will be determined. Second, the Hofbauer cell- specific contribution to the altered inflammatory profile, as is observed in the placenta following pathological prenatal inflammation, will be modeled in in vitro and in vivo models using pathogen-associated molecular patterns (PAMP) stimulation. This project recognizes the complex dynamics of contribution to inflammation and considers all cell types, and their spatial distribution, within the placenta in inflammatory contribution. Thus, spatially resolved techniques will be used to study the Hofbauer cell contribution to inflammation. Our models include primary cell suspensions combined with a rodent model. Ultimately, this work will contribute to improved understanding of the impact of prenatal inflammation at the maternal-fetal interface, the role of Hofbauer cells in response, and potential for targeted anti-inflammatory therapy. Completing the planned education outlined in goals for fellowship training and this project will contribute to my overall formation as an independent physician scientist with a career in advancing the research and care for women’s health.