Defining the role of maternal cells in fetal and infant immunity to malaria

Malaria remains a major cause of childhood morbidity and mortality worldwide, with an estimated 438,000 deaths per year. Prior work has demonstrated that a mother’s experience with malaria during the pregnancy, specifically infection in the placenta, can affect her child’s susceptibility to malaria during infancy. This is thought to result from fetal exposure to and development of tolerance against malaria antigens. The fetus also acquires a small amount of maternal cells and DNA during pregnancy, known as maternal microchimerism. It was recently found that when a mother has placental malaria during her pregnancy, her infant has a larger amount of maternal microchimerism at delivery. In addition, it was found that children with maternal microchimerism at delivery were more likely to become infected with malaria, but when infected, were less likely to become sick or to be hospitalized as compared to children without maternal microchimerism. This finding is suggestive of “natural” vaccination whereby children experience infection but are protected from disease.

These findings led to the hypothesis that in malaria endemic settings, the fetus acquires a maternal graft enriched for malaria-specific cells that allows experience of malaria infection while limiting immune-mediated disease. Using two new cohorts from Uganda and Mali, the investigators propose to isolate and determine the identity and maintenance of the maternal cells in infant blood at delivery and during the first two years of life. In addition, the study will determine if the maternal cells are malaria-specific themselves or, alternatively, if they coordinate the fetal or infant responses against malaria. It is anticipated that this project will demonstrate that in malaria endemic settings, the fetus acquires a maternal graft enriched for regulatory immune cells which are both persistent and malaria-specific. If so, this would be the first demonstration of inherited maternal immune memory and would have broad implications for other perinatal infections, post-natal infections, and response to immunization.

Basic Science
Epidemiology
Immunology

Sep 2017 — Jun 2018

Mali
Uganda