# Mechanisms regulating fetal membrane and neutrophil responses to infection

> **NIH AI R01** · YALE UNIVERSITY · 2026 · $703,356

## Abstract

Summary/Abstract
Chorioamnionitis - inflammation of the fetal membranes (FM) - is characterized by neutrophil infiltration and is
a major risk factor for preterm birth. Even in the absence of prematurity, chorioamnionitis can be detrimental to
the fetus. Despite a strong association between bacterial infection, chorioamnionitis, and preterm birth, the
mechanisms involved are not fully understood. Through expression of the innate immune pattern recognition
receptors (PRR), Toll-like receptors (TLRs) and Nod-like receptors (NLRs), FMs have strategies to evade and
protect against infection. However, depending upon the nature of signaling and regulation, these protective
immune mechanisms may create an inflammatory milieu that can contribute to pathology. In particular, IL-8 is a
major neutrophil chemoattractant and inflammasome-mediated IL-1b is a major inducer of tissue injury and
mediator of preterm birth. We have found that the chorionic compartment is the primary site of FM IL-8 and IL-
1b production in response to bacterial lipopolysaccharide (LPS), peptidoglycan (PDG), and muramyl dipeptide
(MDP) which activate TLR4, TLR2, and Nod2, respectively. While TLRs and NLRs can directly activate
signaling pathways leading to inflammatory cytokine/chemokine production, there is the potential for far more
complex modulation, regulation, and fine-tuning of these processes and the type of responses generated,
particularly for IL-1b. This grant focusses on the requirement of two or more PRRs to be activated sequentially
in FMs exposed to bacterial triggers via novel intermediates. A non-classical family of microRNAs (miRs)
activate the ssRNA sensors, TLR7 and TLR8, to elicit an inflammatory response. These miRs can also be
carried in exosomes and delivered to TLR7 or TLR8 in target cells. Our preliminary data supports the concept
that TLR8-activating miR-146a-3p may acts as a novel intermediate signal that drives FM chemotactic and
inflammatory responses to bacterial TLR and 

## Key facts

- **NIH application ID:** 11249135
- **Project number:** 5R01AI181779-03
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Vikki M Abrahams
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** AI
- **Fiscal year:** 2026
- **Award amount:** $703,356
- **Award type:** 5
- **Project period:** 2024-02-09T00:00:00 → 2028-12-31T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11249135

## Citation

> US National Institutes of Health, RePORTER application 11249135, Mechanisms regulating fetal membrane and neutrophil responses to infection (5R01AI181779-03). Retrieved via AI Analytics 2026-07-12 from https://api.ai-analytics.org/grant/nih/11249135. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*