# Coxiella burnetii Subversion of Host Nrf2 Antioxidant Signaling- Resubmission

> **NIH NIH R21** · UNIV OF ARKANSAS FOR MED SCIS · 2020 · $223,990

## Abstract

Coxiella burnetii is the intracellular bacterial agent of human Q fever, an acute flu-like illness that can
present as potentially fatal chronic endocarditis. Mechanisms used by C. burnetii to parasitize human
macrophages remain a mystery. However, through the use of other cell models, studies have
demonstrated that C. burnetii regulates numerous host processes, including vesicular trafficking and
apoptosis. The current proposal is designed to define mechanisms used by C. burnetii to avoid
the oxidative stress response of human alveolar macrophages, which are the pathogen’s
target cell in vivo. We found that C. burnetii triggers activation of the cargo receptor p62 and
potentially uses this versatile protein to activate the antioxidant transcription factor Nrf2. Aim 1 is
designed to define the mechanism by which p62 activates Nrf2. Aim 2 will define the downstream
impact of Nrf2 activation on C. burnetii prevention of the oxidative stress response and apoptosis.
Throughout the proposal, we will use our primary human alveolar macrophage model of infection to
identify disease relevant processes. Collectively, the aims in the current proposal will provide
needed insight into the mechanisms used by C. burnetii to parasitize human macrophages,
which is a prerequisite for progression of Q fever.

## Key facts

- **NIH application ID:** 10056597
- **Project number:** 1R21AI144508-01A1
- **Recipient organization:** UNIV OF ARKANSAS FOR MED SCIS
- **Principal Investigator:** Daniel E Voth
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $223,990
- **Award type:** 1
- **Project period:** 2020-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10056597

## Citation

> US National Institutes of Health, RePORTER application 10056597, Coxiella burnetii Subversion of Host Nrf2 Antioxidant Signaling- Resubmission (1R21AI144508-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10056597. Licensed CC0.

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