# Exploiting a cyclic dinucleotide-mediated immune response to reduce the burden of Coxiella burnetii infection

> **NIH NIH R01** · WASHINGTON STATE UNIVERSITY · 2022 · $466,870

## Abstract

Project Summary/Abstract:
 Cyclic dinucleotides (CDNs) play important second messenger roles in Gram-negative bacteria,
regulating a number of different types of bacterial processes such as motility, biofilm formation, host
colonization, bacterial growth, and metabolism. CDNs levels are tightly controlled by bacterial encoded
diguanylate/diadenylate cyclases and phosphodiesterases. In addition to regulating bacterial life cycle
processes, CDNs can alert the innate immune response during infection. A major cytosolic sensor for
intracellular CDNs in animal hosts is STING, which upon its activation, triggers an innate immune response
through the induction of type I interferon and pro-inflammatory cytokines. As such, synthetic CDNs have been
applied exogenously prior to infection to stimulate inflammasome activity and reduce the load of Chlamydia
trachomatis, a Gram-negative, obligate intracellular bacterium. Thus CDNs can be used to initiate an immune
response to therapeutically treat Chlamydia infection, in addition to standard two-week antibiotic therapy.
 Another Gram-negative, obligate intracellular, macrophage-tropic bacterium is Coxiella burnetii, which
is the causative agent of the zoonotic disease Q fever. The primary route of Coxiella transmission is through
aerosols. However, Coxiella is also found in ticks, and they have been implicated as vectors. Acute phase of
the disease in humans is characterized primarily by influenza-like symptoms, and individuals that develop
chronic infection must undergo 18-24 months of antibiotic therapy. We contend that alternative methods to
current antibiotic treatments need to be developed to reduce Coxiella load in infected animals. Our preliminary
data suggests that CDNs are produced during Coxiella infection and that the Coxiella genome contains
putative genes that encode diguanylate/diadenylate cyclases and phosphodiesterases. However, little is known
about how CDNs elicit a STING-mediated host response during Coxiella infection. Thus, we propose to
determine how CDNs control the innate immune response to Coxiella burnetii infection. In Aim 1, we will
characterize the STING-mediated host response to Coxiella infection in vertebrate and invertebrate models. In
Aim 2, we will dissect STING's mechanism of action during Coxiella infection with regard to caspase activation
and programmed cell death. In Aim 3, we will stimulate the host innate immune response with CDNs in
vertebrate and invertebrate models to reduce the magnitude of Coxiella infection.
 Together, the proposed work will characterize the CDN-mediated innate immune response to Coxiella
infection and how we can exploit CDNs to reduce overall Coxiella burden. The use of invertebrate models of
Coxiella infection may be applicable to other vector-borne diseases. The information gained in this study will
have broad-ranging impacts in innate immunity towards to the development of new therapies to treat Coxiella
infection, and we will identify potentia...

## Key facts

- **NIH application ID:** 10406352
- **Project number:** 5R01AI139051-04
- **Recipient organization:** WASHINGTON STATE UNIVERSITY
- **Principal Investigator:** Alan Gabriel Goodman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $466,870
- **Award type:** 5
- **Project period:** 2019-07-23 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10406352

## Citation

> US National Institutes of Health, RePORTER application 10406352, Exploiting a cyclic dinucleotide-mediated immune response to reduce the burden of Coxiella burnetii infection (5R01AI139051-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10406352. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*