# Impact of early microbial exposure on immune ontogeny

> **NIH NIH R01** · CORNELL UNIVERSITY · 2022 · $349,124

## Abstract

Project Summary / Abstract
Evidence has shown that microbial exposure during critical stages of development can have long-lasting effects
on the health status of an individual. However, there is currently no conceptual framework to explain how
maternal microbial exposure shapes the fetal and adult immune systems. To fill this knowledge gap, we have
developed a novel pet-shop mouse model and compared the ontogeny of CD8+ T cells in mice that were born
from either ‘clean’ (SPF) or ‘dirty’ (pet-shop) mothers. Interestingly, the mice raised in the dirty environment
mounted a more robust CD8+ T cell response and were highly resistant to infection. To understand how the
ontogeny of the CD8+ T cell compartment was altered in the dirty mice, we used fate-mapping ‘timestamp’ mice
and found a higher proportion of fast-acting fetal derived CD8+ T cells and fewer slow-acting adult derived CD8+
T cells present in the dirty mice. We also found that immune susceptibility could be normalized between clean
and dirty mice by depleting the fetal layer of CD8+ T cells. These data indicate that maternal microbial exposure
leads to an accumulation of fetal-derived CD8+ T cells that protects the host against intracellular pathogens.
However, the underlying mechanisms remain undefined. Our hypothesis is that maternal microbial exposure
alters developmental layering in the offspring by changing the dynamics of cell survival and peripheral selection
of T cell receptors. In the first aim, we will combine our fate mapping approach with mathematical modeling to
understand how maternal microbial exposure leads to an accumulation of fetal-derived CD8+ T cells. In the
second aim, we will use paired single cell TCR/RNAseq to understand how the maternal microbial environments
alters the TCR repertoire and immune defense. Knowledge gained from these studies is expected to provide a
new conceptual model for understanding how maternal microbial colonization in early life can permanently
program the offspring’s immune system and life-long disease risk.

## Key facts

- **NIH application ID:** 10494180
- **Project number:** 5R01HD107798-02
- **Recipient organization:** CORNELL UNIVERSITY
- **Principal Investigator:** Miles Philip Davenport
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $349,124
- **Award type:** 5
- **Project period:** 2021-09-24 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10494180

## Citation

> US National Institutes of Health, RePORTER application 10494180, Impact of early microbial exposure on immune ontogeny (5R01HD107798-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10494180. Licensed CC0.

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