Mapping the spatial and functional response of placental macrophages to group B streptococcus infection

Active Project Grant Awarded Last action

Award ID
F30HD122394
Recipient
Awarding agency
Obligated
$91,326

Award facts

Completion date 0% complete
Originally
Place of performance
Chicago, IL 60611, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
Streptococcus agalactiae (group B streptococcus, GBS) infection is a major cause of pregnancy-related complications, including preterm labor, stillbirth, and early-onset neonatal sepsis. GBS is a gram-positive bacterium that asymptomatically colonizes the vaginal tract of 25% of women, but can ascend during pregnancy, cross into the amnionic cavity to infect the placenta, and transmit to the fetus. The placental membranes, which surround the fetus in utero as a physical and immune barrier, can become inflamed in response to bacterial infection. Inflammation in pregnancy is a delicate balance, promoting immune tolerance to the fetus while maintaining the capacity to defend against pathogens. Macrophages are resident immune cells in the placenta membrane and the initial responders to GBS infection. CO-cultured placental macrophages receive immunosuppressive stimuli from structural placental membrane cells yet are still capable of response to GBS in vitro. Additionally, macrophages can be of maternal or fetal origin, but fetal macrophages in the placental membranes are not well characterized. Elucidating the mechanism by which macrophages activate in response to GBS within the spatial context of the placental membrane is a necessary step towards the detection and prevention of bacterial-induced preterm labor and neonatal sepsis, and can be investigated with the combination of imaging and spatial transcriptomic data. Our overarching hypothesis is that maternal and fetal macrophages in the placental membrane differ in initial polarization and response to GBS, and the extent of macrophage activation is influenced by spatial proximity to bacteria and neighboring cells. In aim 1, I will spatially define and quantify placental macrophage recruitment in response to GBS infection using machine learning and digital pathology techniques. I will measure macrophage density, localization, and morphology within the placental membrane, comparing the response in GBS cases to controls. In aim 2, I will measure the functional response of placental macrophages to GBS organisms present in the membranes using spatial transcriptomics. Sub-aim 2A will assess macrophage polarization and local cellular interactions in the presence of GBS bacteria, while sub-aim 2B will leverage genetic differences to distinguish maternal and fetal macrophage subpopulations and their contributions to the GBS immune response. The success of this project will establish foundational knowledge in the innate immune response to bacterial GBS infection during pregnancy. My long-term goal is independent, impactful work in reproductive sciences using machine learning, placental biology, and multiomics technology to improve reproductive health and enhance the lives of children. To accomplish this goal, I have brought together a mentorship network of experts and carefully selected training activities, providing me with the support and cutting-edge skillset necessary to mature as an independent physician-scientist in reproductive sciences.

Transactions

Action Obligated Date
Amendment $45,663
Amendment $45,663
Original award $0

Quick answers

Who received award F30HD122394?

F30HD122394 was awarded to Northwestern University by National Institute of Child Health and Human Development (National Institutes of Health) on December 1, 2026.

How much is award F30HD122394 worth?

$91,326 has been obligated on F30HD122394.

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