# Intracellular IL-17 signaling during Coxiella burnetii infection

> **NIH NIH R21** · UNIVERSITY OF NEBRASKA MEDICAL CENTER · 2021 · $191,250

## Abstract

PROJECT SUMMARY/ABSTRACT
Coxiella burnetii is an obligate intracellular bacterium and the etiological agent of Q fever. During natural infection
Coxiella targets alveolar macrophages, where the bacterium promotes formation of a phagolysosome-like
vacuole called the Coxiella Containing Vacuole (CCV). Successful host cell infection requires the Type IVB
Secretion System (T4BSS), which translocates bacterial effector proteins across the CCV membrane and into
the host cytoplasm, where they manipulate a variety of cell processes. We recently demonstrated that the
Coxiella T4BSS downregulates expression of IL-17 target genes as well as IL-17-stimulated chemokine
secretion. IL-17 is a pro-inflammatory cytokine that has a key role in the innate immune response against
pulmonary pathogens. Upon IL-17 binding, the macrophage surface IL-17 receptor activates several intracellular
signaling pathways through the E3-ubiquitin ligase ACT1. ACT1 ubiquitinates TRAF6, triggering transcriptional
activation of IL-17 target genes. The proposed experiments will test our hypothesis that Coxiella T4BSS effector
proteins downregulate intracellular IL-17 signaling pathway(s) in order to evade the host innate immune response
and promote bacterial pathogenesis. Aim 1 will determine the host and bacterial proteins involved in
downregulation of intracellular ACT1-TRAF6 signaling pathways triggered by IL-17. Aim 2 will elucidate the role
of IL-17 signaling in chemokine secretion and neutrophil recruitment to Coxiella-infected macrophages.
Completion of these studies will not only reveal a specific host innate immune response used against C. burnetii,
but also a novel strategy employed by pathogens to escape the immune response during the initial stages of
infection.

## Key facts

- **NIH application ID:** 10201507
- **Project number:** 5R21AI149723-03
- **Recipient organization:** UNIVERSITY OF NEBRASKA MEDICAL CENTER
- **Principal Investigator:** STACEY D GILK
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $191,250
- **Award type:** 5
- **Project period:** 2020-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10201507

## Citation

> US National Institutes of Health, RePORTER application 10201507, Intracellular IL-17 signaling during Coxiella burnetii infection (5R21AI149723-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10201507. Licensed CC0.

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