# Role of Hofbauer Cells in Fetal Infection/Inflammation

> **NIH NIH R01** · YALE UNIVERSITY · 2020 · $413,817

## Abstract

Fetal inflammation and infcetion remains a major cause of neonatal mortality and morbidity. Our previous
studies showed that histological chorioamnionitis (HCA), microbial-driven infiltration of leukocytes to the
maternal-fetal interface, was associated with a focal increase in the number of Hofbauer cells (HBCs) (i.e.
placental macrophages of fetal origin located beneath the syncytium and adjacent to fetal capillaries), in the
placental villus. Elucidation of cell type-specific responses to polymicrobial challenges would lead to new
interventions which reduce the incidence of and/or severity of adverse outcomes including fetal-inflammatory
response syndrome (FIRS), a multisystemic/microbial-driven inflammation in the umbilical cord (funisitis) and
fetus, which is associated with significant neonatal/pediatric mortality and morbidity. Microbial compounds
trigger innate immune response through Toll-like receptors (TLRs), and TAMs, a recently characterized
subfamily of protein tyrosine kinase receptors shown to inhibit TLR function in non-placental cell types. In
addition, inflammatory response to microbes is regulated through the inflammasome, a multi-protein complex.
Our central hypothesis is that herpes virus infection of HBCs suppresses their inflammatory responses to
bacteria by altering TAM receptor and Nalp3 inflammasome function, thus inhibiting HBCs' ability to control
bacterial growth and, therefore, exacerbating placental/fetal infection, and chorioamnionitis. Our Specific Aims
will: 1) Test the hypothesis that herpes virus infection of HBCs blocks LPS-induced TNF-α and IL-1β through
modification of the expression and function of TAM receptors and the Nalp3 inflammasome; 2) Test the
hypothesis that HV infection of HBCs increases TAM receptor function and inhibits inflammasome activity
which promotes the migration and colonization of bacteria to the fetus; 3) Test the hypothesis that a
polymicrobial herpes virus-bacterial infection increases placental macrophages with a suppressed
inflammatory phenotype in vivo, promoting the migration of bacteria from mother to the fetus.

## Key facts

- **NIH application ID:** 9980782
- **Project number:** 5R01AI131613-04
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Vikki M Abrahams
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $413,817
- **Award type:** 5
- **Project period:** 2017-08-17 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9980782

## Citation

> US National Institutes of Health, RePORTER application 9980782, Role of Hofbauer Cells in Fetal Infection/Inflammation (5R01AI131613-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9980782. Licensed CC0.

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