# Project 3: Negative regulation of type I interferons during bacterial infection

> **NIH NIH P01** · UNIVERSITY OF CALIFORNIA BERKELEY · 2024 · $434,094

## Abstract

Project Summary/Abstract (Project 3, Vance)
Intracellular bacterial pathogens remain a major cause of human mortality and morbidity. By working
collaboratively with other P01 Projects, we focus in Project 3 on the role of type I interferons (IFNs) in the
innate immune response to three intracellular bacterial pathogens: Listeria monocytogenes, Mycobacterium
tuberculosis, and Legionella pneumophila. As we and others have shown previously, all three pathogens
induce the expression of type I IFNs via the STING pathway. However, while type I IFNs are generally
accepted to play a crucial role in orchestrating anti-viral immunity, the roles of type I IFNs in the responses
to bacteria are complex. Indeed, our work and that of other laboratories has shown that type I IFNs tend to
exacerbate infection by bacterial pathogens, including M. tuberculosis, L. pneumophila and L.
monocytogenes. Our preliminary data suggest that type I IFN-dependent induction of the interleukin-1
receptor antagonist (IL-1Ra) is an important mechanism by which type I IFNs exacerbate bacterial
infections. Our preliminary data also suggest the existence of regulatory pathways to prevent the adverse
induction of type I IFNs during bacterial infections. We identify SP140 and MORC3 as two novel negative
regulators of type I IFN expression. We propose three Aims to explain why type I IFNs hinder anti-bacterial
immunity and to explain how interferons are normally properly regulated during bacterial infections, in both
mice and humans. In Aim 1, we test the hypothesis that type I IFNs antagonize anti-bacterial immunity via
induction of IL-1 receptor antagonist, and determine the underlying mechanism. In Aim 2, we dissect the
mechanism by which SP140 negatively regulates type I IFN transcription during bacterial infections. In Aim
3, we identify and characterize MORC3 as a novel negative regulator of type I IFN in human cells, and
determine its function during bacterial infection.

## Key facts

- **NIH application ID:** 10885137
- **Project number:** 5P01AI063302-21
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** RUSSELL E VANCE
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $434,094
- **Award type:** 5
- **Project period:** 2004-09-30 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10885137

## Citation

> US National Institutes of Health, RePORTER application 10885137, Project 3: Negative regulation of type I interferons during bacterial infection (5P01AI063302-21). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10885137. Licensed CC0.

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