The developing fetal immune landscape and congenital viral infection

Fetal development is a complex process that can lead to adverse health consequences when impaired, such as congenital anomalies, fetal growth restriction, preterm birth, and stillbirth. Although there is a well-developed literature on the timing of adaptive immune cell appearance in the fetus, comparatively little is known about the ontogeny and functional maturation of the innate immune system over gestation. This knowledge gap limits our understanding of how intrauterine infections influence fetal development and contribute to adverse obstetric and neonatal outcomes. Thus, the goal of this review is to summarize existing knowledge of the ontogeny of the fetal adaptive and innate immune systems throughout gestation, and how they are impacted by infection. We examine the emergence of hematopoietic stem and progenitor cells, while highlighting changes in immune lineages across the fetal brain, liver, thymus, bone marrow, spleen, and placenta, which play critical roles in immune competency and tolerance. The role of innate immunity in immunocompetence and pathogen responses is highlighted when known. Finally, we address how vertically transmitted and teratogenic viral infections disrupt normal immune and tissue development. Collectively, these studies demonstrate the dynamic, tissue-specific immune landscape that evolves throughout gestation.