# Intracellular IL-17 signaling during Coxiella burnetii infection

> **NIH NIH R21** · UNIVERSITY OF NEBRASKA MEDICAL CENTER · 2020 · $184,510

## 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 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.
Further, the Coxiella T4BSS confers protection against IL-17 mediated killing by the macrophage. 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. Unphosphorylated ACT1 ubiquitinates TRAF6, triggering transcriptional activation
of IL-17 target genes, while phosphorylated ACT1 recruits TRAF2/5, binds to the 3’ mRNA of IL-17 target genes
and stabilizes the mRNA for translation. 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 whether Coxiella targets the ACT1-TRAF6
pathway to downregulate IL-17 target gene transcription. Aim 2 will test whether Coxiella destabilizes the mRNA
of IL-17 target genes through ACT1-TRAF2/5. 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:** 10295139
- **Project number:** 7R21AI149723-02
- **Recipient organization:** UNIVERSITY OF NEBRASKA MEDICAL CENTER
- **Principal Investigator:** STACEY D GILK
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $184,510
- **Award type:** 7
- **Project period:** 2020-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10295139

## Citation

> US National Institutes of Health, RePORTER application 10295139, Intracellular IL-17 signaling during Coxiella burnetii infection (7R21AI149723-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10295139. Licensed CC0.

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