# The Role of macrophages in chorioamnionitis and group B streptococcal infections

> **NIH NIH R01** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2020 · $472,582

## Abstract

Chorioamnionitis (CAM), or inflammation of the fetal membranes, is often the result of ascending bacterial
infection and is a major contributor to premature birth, neonatal sepsis, and long-term disability and morbidity
in babies. Unfortunately, CAM is often asymptomatic and not easily diagnosed in time to prevent maternal and
fetal adverse outcomes. Solving this problem is hamstrung by a limited understanding of early steps in disease
pathogenesis. Despite its relatively simple structure, surprisingly little is known about how fetal membranes
participate in immune defense against potential pathogens. Defining the cellular and molecular basis of innate
immunity within the membranes promises to reveal actionable, host-based targets for diagnosis, prevention
and therapy against CAM. Our objective is to define specific contributions of macrophages to fetal membrane
immunology in the context of bacterial CAM caused by the common pathogen Group B Streptococcus (GBS).
Macrophages in the gravid uterus balance host defense activities with pregnancy-specific actions such as
promoting placental development and governing immune tolerance between mother and fetus. It is fascinating
that both maternal (decidual) and fetal (placental) macrophages are present at the maternal-fetal interface, yet
their specific roles in innate immunity are unknown. We hypothesize (1) that maternal and fetal macrophages
make unique contributions both to host defense and tissue inflammatory responses during bacterial infection
and (2) that the common CAM pathogen, GBS, evades innate immunity by resisting the oxidative stress within
these macrophages. We will test this hypothesis through three Aims. In Aim 1 we will determine the extent to
which maternal and fetal macrophages contribute to the natural history of CAM in vivo using a model of
ascending GBS infection. In Aim 2 we will identify the extent to which GBS survival within macrophages
depends upon the NADH peroxidase (npx) or other genotype-specific intracellular survival defenses.
Mutagenesis studies will be conducted to better understand the impact of npx and other GBS mutations on
survivability and disease in vivo, and to classify bacterial and host genes important for the process using RNA
sequencing. Additional genotypes will be examined for variation in the ability to survive inside decidual and
placental macrophages and persist in the presence of antibiotics commonly used to treat GBS infections.
Lastly, in Aim 3 we will define the paracrine contribution of macrophages within the human fetal membrane
during infection. For this aim, we will take a deconstructive approach, populating a microfluidic, instrumented
fetal membrane-on-chip with decidual or placental macrophages, decidual stromal cells, trophoblasts and
amnion epithelial cells. We will test the sub-hypothesis that distinct macrophage types contribute uniquely to
inflammatory quiescence within uninfected membranes and amplify proinflammatory responses upon mic...

## Key facts

- **NIH application ID:** 9978691
- **Project number:** 5R01AI134036-04
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** David M Aronoff
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $472,582
- **Award type:** 5
- **Project period:** 2017-08-18 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9978691

## Citation

> US National Institutes of Health, RePORTER application 9978691, The Role of macrophages in chorioamnionitis and group B streptococcal infections (5R01AI134036-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9978691. Licensed CC0.

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