Understanding the Immunological Changes That Occur During Pregnancy
Premature birth and other pregnancy complications remain the leading cause of mortality in children each year. Infections in pregnant mothers and neonates also contribute to this alarming epidemic of neonatal deaths. The Erickson lab studies the immunological changes that occur during pregnancy that enhance neonatal immune defense against pathogens causing serious life-threatening infections, while also promoting tolerance between the maternal immune system and developing baby to prevent pregnancy complications.
A common thread connecting these two immunological mandates are the subtle molecular changes that occur on sugar molecules attached to proteins, scientifically referred to as N-linked glycosylation. We recently uncovered a surprising mechanism employed during pregnancy that enables antibodies to protect against intracellular infections. Unfortunately, pregnant women and newborns are at high risk of infections caused by intracellular pathogens, largely because they “hide” from antibodies by staying inside of cells. However, studying these infections through the more physiologically relevant lens of pregnancy and neonatal infection revealed that antibodies indeed do protect babies against intracellular infections. The reason is that the maternal immune system makes an extremely subtle change to the sugars attached to antibodies, which is all it takes to transform an infection with 90% mortality in neonatal mice to one with 90% survival. We determined that this subtle molecular switch works by enabling the maternal antibodies to bind to the sialic acid receptor CD22 on neonatal B cells, which in turn shuts off the production of the immunosuppressive cytokine IL-10. These results were recently published in Nature and were highlighted as a key discovery in the Cincinnati Children's Research Annual Report.
Interestingly, maternal B cells also express CD22, and proteins that come from the placenta and baby possess sugars that can bind to CD22. Given how powerfully CD22 regulates B cells during neonatal infections, we are now seeking to understand if CD22 also regulates B cells during pregnancy to promote tolerance of the maternal immune system towards the developing fetus. Together, these different research approaches are aimed at reducing the silent epidemic of neonatal mortality and improving the health of children worldwide.
