# Mechanisms of particulate matter driven infant respiratory disease

> **NIH NIH R01** · TEXAS A&M UNIVERSITY · 2020 · $396,316

## Abstract

Project Summary
Intrauterine exposure to ambient particulate matter (PM) air pollution has been associated with increased lower
respiratory tract infections (LRTIs) in infants. Despite the known sensitivity of the fetus to environmental
pollutants and epidemiological evidence correlating prenatal PM exposure and LRTI morbidity, mechanisms of
PM enhanced pathogenesis are relatively unexplored in immunologically immature populations. Preliminary
data from our novel intrauterine murine exposure model demonstrate the reduced ability of immature offspring
exposed to PM in utero to develop a robust inflammatory response. Based on these data and similar results in
our neonatal (i.e., <7 days of age) exposure model indicating increased respiratory infection severity following
early life exposure to air pollution, we hypothesized this window of immunosuppression correlates with
offspring susceptibility to severe respiratory syncytial virus (RSV) disease. RSV infection represents a
significant cause infant respiratory morbidity and mortality. Its pathogenesis is known to be impacted by similar
pathways affected by PM-induced oxidative stress, namely the nuclear factor erythroid 2-related transcription
factor (Nrf2) antioxidant response pathway. Polymorphisms impacting maternal Nrf2 signaling have recently
been reported to increase LRTI risk in infants exposed to PM in utero. Thus, to test our hypothesis and clarify
the impact of maternal ability to respond to oxidative stress on offspring RSV disease severity, we will carry out
two specific aims in the proposed project. In Aim 1, we will combine our novel intrauterine exposure model with
our well-characterized neonatal mouse model of RSV infection to characterize RSV infection severity.
Specifically, we will determine how altered pulmonary T cell profiles influence offspring adaptive immune
responses. In Aim 2, we will use Nrf2-deficient and wild-type mice to investigate the role of maternal Nrf2
expression on offspring pulmonary oxidative stress responses to intrauterine PM and RSV susceptibility. We
will further probe the protective role of Nrf2 through maternal dietary supplementation with a known Nrf2
inducer. Outcomes from this research will provide important insight to understand interactions between genetic
and environmental determinants of immunopathogenesis of RSV infection. These findings will aid in identifying
susceptible subgroups of children and establish the proof-of-principle for targeting the Nrf2 response pathway
in mothers exposed to air pollution for the protection against childhood respiratory disease, a pervasive public
health problem affecting millions of children worldwide.

## Key facts

- **NIH application ID:** 9830652
- **Project number:** 5R01ES028866-03
- **Recipient organization:** TEXAS A&M UNIVERSITY
- **Principal Investigator:** Natalie M Johnson
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $396,316
- **Award type:** 5
- **Project period:** 2017-12-15 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9830652

## Citation

> US National Institutes of Health, RePORTER application 9830652, Mechanisms of particulate matter driven infant respiratory disease (5R01ES028866-03). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9830652. Licensed CC0.

---

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