# Role of Microbiome in Neonatal Lung Maturation and Immune Susceptibility

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2020 · $554,328

## Abstract

ABSTRACT
Infants are more susceptible to morbidity and mortality in response to respiratory virus infections as compared
with school age children or adults, but the mechanisms for this clinical observation are not well understood.
Vulnerability to respiratory viruses during infancy is likely manifested by an immature lung and immune system.
The ability to establish robust protective immunity during infancy is partly limited by developmental shifts in
hematopoietic cell function, yet the immune cells that reside within the neonatal lung remain poorly
characterized. Even less is known about the epithelial cells of the neonatal lung which could contribute to the
immunocompromised state of the human infant given their role in communicating environmental signals to the
adaptive immune system. Lastly, how the establishment of commensal bacteria at mucosal sites might
influence the immature lung and immune system remains undetermined. Our overall goal is to understand the
cellular and molecular mechanisms for increased respiratory disease susceptibility during the first year of life.
We will investigate the contribution of primary commensal colonization in the neonatal lung on severity of
respiratory virus infection using an infant rhesus monkey model of influenza infection. We hypothesize that
primary commensal colonization in the neonatal lung is essential for development of antiviral defense during
early life. To test our hypothesis, we will (1) Characterize the influence of primary commensal colonization in
the airways on the severity of influenza infection; (2) Investigate how primary commensal colonization directs
the ontogeny and functional development of ILC3. (3) Determine if primary commensal colonization alters the
intrinsic transcriptome profile of infant airway epithelium. The limitations of early life immunity present
formidable obstacles for effective therapeutic strategies that provide protection against respiratory pathogens
in the infant. We anticipate that our collaborative effort to study a translational animal model of neonatal
development will bring forth new paradigms in understanding mucosal immunity in the infant that have the
potential for durable impact on human health.

## Key facts

- **NIH application ID:** 9879678
- **Project number:** 5R01AI138553-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Lisa A Miller
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $554,328
- **Award type:** 5
- **Project period:** 2018-03-19 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9879678

## Citation

> US National Institutes of Health, RePORTER application 9879678, Role of Microbiome in Neonatal Lung Maturation and Immune Susceptibility (5R01AI138553-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9879678. Licensed CC0.

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