# Role of IFNs and IFNGR in susceptibility to bacteria in Down syndrome

> **NIH NIH R21** · UNIVERSITY OF COLORADO DENVER · 2022 · $190,965

## Abstract

Project Summary
Activated myeloid cells promote host resistance to infections but also drive inflammation that can damage
tissue and contribute to chronic diseases. Thus, the immune system must carefully balance responses that
regulate myeloid cell accumulation and activation – ideally optimizing protective responses against infectious
agents while limiting inflammatory responses. We believe an improved understanding of how myeloid cell
activity is regulated will aid development of therapies that more specifically target excessive inflammation
while preserving protective anti-microbial myeloid cell activities. This proposal specifically focuses on a
mechanism by which type I IFNs suppress myeloid cell responses and addresses whether such suppression
contributes to increased host susceptibility in a murine model for Down syndrome, the Dp16 mouse.
Type I interferons (IFNs) induce an antiviral state that is protective against viruses, but these cytokines also
have immune regulatory functions and are used in clinical contexts to treat inflammation-associated disease.
Further, in a number of bacterial infections type I IFNs are associated with increased host susceptibility. Our
lab and others have previously demonstrated that these “pro-bacterial” effects of type I IFNs correlate with
dampening of myeloid cell anti-microbial activation. Here, we investigate the impact of type I IFNs and
IFNGR1 down regulation in myeloid cells on resistance/susceptibility in the context of a chromosomal
triplication in mice that mimics trisomy 21 in humans. Results of these efforts could advance host-directed
therapies to counter the silencing of Ifngr1 for boosting immune responses in individuals with DS and severe
bacterial infections, including infections by pathogens that are resistant to conventional antibiotics.

## Key facts

- **NIH application ID:** 10356944
- **Project number:** 5R21AI161827-02
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Laurel L Lenz
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $190,965
- **Award type:** 5
- **Project period:** 2021-02-22 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10356944

## Citation

> US National Institutes of Health, RePORTER application 10356944, Role of IFNs and IFNGR in susceptibility to bacteria in Down syndrome (5R21AI161827-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10356944. Licensed CC0.

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