# The Effect of Maternal Cells on Infant Immunity

> **NIH NIH K08** · SEATTLE CHILDREN'S HOSPITAL · 2020 · $170,725

## Abstract

PROJECT SUMMARY
Despite large improvements in global childhood mortality in the last 20 years, an astonishing 5.9 million
children died before their fifth birthday in 2015. Three of the top five causes of death are infectious, including
pneumonia, diarrhea, and neonatal sepsis. Although extrinsic factors such as vaccination, access to clean
water, antibiotics, and accurate diagnostics are targets of current public health campaigns, little is known about
the host intrinsic factors that affect susceptibility to these illnesses. In particular, thus far overlooked is the role
of a small number of maternal cells and DNA acquired by the fetus during pregnancy, known as maternal
microchimerism, in infant infection. This proposal specifically seeks to understand the role of these maternal
cells in shaping fetal and infant immune responses and subsequent protection from infectious diseases during
childhood. We recently 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 may imply a mechanism of natural
“vaccination” whereby children experience infection but are protected from disease. We hypothesize that this
effect is the result of maternal regulation of pro-inflammatory fetal and infant immune responses, limiting
immune-mediated pathology, and that such regulation may extend to immune responses directed against other
infections of global health importance. Using samples and data from a birth cohort from Mali, we propose to
identify the factors that determine the acquisition of maternal microchimerism, the ability of maternal cells to
modulate the immune phenotype of the fetus and infant, and the role of maternal cells in protection from
common childhood infections, including pneumonia and diarrhea. We anticipate that this study will demonstrate
that acquired maternal cells influence fetal and infant immune responses, which would have broad implications
for perinatal and postnatal infections and response to immunization. In addition, demonstrating that maternal
cells provide protection against childhood infections would suggest an evolutionary benefit to maintaining this
graft, emphasizing the importance of intergenerational immune interactions. Finally, identification of the factors
that predict maternal microchimerism may lead to future targets for intentional modulation of maternal cells as
a novel approach to prevent the immune-mediated morbidity and mortality associated with childhood infections
of global health importance.

## Key facts

- **NIH application ID:** 9828750
- **Project number:** 5K08AI135072-03
- **Recipient organization:** SEATTLE CHILDREN'S HOSPITAL
- **Principal Investigator:** Whitney Elizabeth Harrington
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $170,725
- **Award type:** 5
- **Project period:** 2017-12-12 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9828750

## Citation

> US National Institutes of Health, RePORTER application 9828750, The Effect of Maternal Cells on Infant Immunity (5K08AI135072-03). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/9828750. Licensed CC0.

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