# Age-dependent susceptibility to infection

> **NIH NIH F32** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2021 · $66,390

## Abstract

Project Summary
Acute respiratory infections (ARI), which generally begin with colonization of the mucosal surfaces of the
upper respiratory tract (URT), are a leading cause of morbidity with the highest rate in infants. Both the
incidence and duration of URT carriage with common respiratory pathogens declines in adults. Despite
substantial evidence linking young age to ARI, identification of age-dependent factors that enhance
acquisition and delay clearance of respiratory pathogens have largely been unexplored. Currently, a major
obstacle in determining age-dependent mechanisms arises from the exclusive reliance on adult animal
modeling.
In this study, we will utilize both infant and adult mouse models to determine specific immune mechanisms
that are critical for mediating resistance to URT infections by using S. pneumoniae as a model pathogen.
Using this model, we found that young age predisposes mice to both acquisition and carriage of S.
pneumoniae infection. To study the underlying effects of age we used RNA-sequencing (RNA-Seq) to
transcriptionally profile and compare the mucosal epithelia of infant and adult mice at baseline (uninfected).
Our preliminary data show an age-dependent alteration of mucosal defense mechanisms, consisting of
dampened expression of ubiquitous antimicrobial molecules and impaired interleukin-1 signaling in infant
mice compared to adult mice. Furthermore, we observed a significant alteration in central metabolism of the
URT indicated by a repression of genes involved in oxidative phosphorylation and peroxisome proliferator
activated receptor (PPAR) signaling. These data indicate a potential regulatory role for metabolic pathways
of mucosal immune defenses. Given these findings we hypothesize that impaired mucosal defense
mechanisms during the neonatal period promote acquisition and stable colonization of URT pathogens,
which facilitate bacterial dissemination and promote development of systemic infection. This hypothesis will
be addressed by the following Specific Aims: (1) to determine how age of the host impacts URT epithelial
barrier defense mechanisms; (2) to characterize the role of interleukin 1 (IL-1) signaling during young age
and (3) to elucidate the role of PPAR signaling in mediating epithelial barrier defense.
These studies will improve our understanding of age-related differences in mucosal defense mechanisms
and facilitate the development of novel therapeutic strategies to protect infants from prevalent URT
pathogens.

## Key facts

- **NIH application ID:** 10102189
- **Project number:** 5F32AI143043-03
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Kristen Lokken-Toyli
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $66,390
- **Award type:** 5
- **Project period:** 2019-03-01 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10102189

## Citation

> US National Institutes of Health, RePORTER application 10102189, Age-dependent susceptibility to infection (5F32AI143043-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10102189. Licensed CC0.

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