# Mechanisms of innate immune-microbial interactions in vocal fold Inflammation

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 2021 · $513,195

## Abstract

Abstract
The larynx is a strategically important organ situated at the crossroads of the upper respiratory and digestive
tracts, orchestrating swallowing, breathing, coughing and, in humans, voice. The hallmark of many clinically
important laryngeal diseases affecting these critical functions is mucosal inflammation. In other parts of the
body, the pathogenesis of mucosal inflammatory disease is intimately linked to local immune responses. The
long-term goal of our research is to improve prevention and management of vocal fold disease by identifying
and manipulating the manner in which epithelial cell-fibroblast interactions modulate healthy and aberrant
mucosal healing following inflammation. In our previous funding period, as a necessary first step to towards
achieving our long term goal, we developed a steady source of stable vocal fold epithelial cells to study
epithelial cell-fibroblast interactions and established a novel physiologically relevant, three-dimensional
biomimetic in vitro vocal fold model of human origin. For the proposed funding period, we will specifically focus
on using a unique combination of in vitro and vivo model systems, including those developed in the previous
funding period, to further our knowledge of host mediated immune defenses and inflammatory based tissue
alterations in the vocal fold mucosa when exposed to defined bacteria species. The overall objective of this
proposal is to identify mechanisms by which resident commensal or pathogen bacterial species are identified
by vocal folds via specialized receptors and control tissue immune homeostasis while promoting immune
responses in the context of steady state and tissue inflammation. In Specific Aim 1, we will define the role of
commensal bacteria in tuning vocal fold immune cells using gnotobiotic methodologies. In Specific Aim 2, we
will identify toll like family receptors (TLR) in vocal fold tissue and novel human vocal fold epithelial cells in
steady state and inflammatory conditions. Lastly, in Specific Aim 3, using our physiologically relevant three-
dimensional biomimetic model of normal and inflammatory vocal fold mucosa, we will determine relative
contribution of resident commensal and pathogenic microbial communities on vocal fold mucosal integrity and
function. Taken together, our multidisciplinary exploitation of microbiology, next gen sequencing, and
immunology will converge to reform exponentially our understanding of mechanisms of innate immune-
microbial interactions in vocal fold inflammatory diseases.
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## Key facts

- **NIH application ID:** 10146837
- **Project number:** 5R01DC012773-09
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Susan Lynn Thibeault
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $513,195
- **Award type:** 5
- **Project period:** 2012-12-07 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10146837

## Citation

> US National Institutes of Health, RePORTER application 10146837, Mechanisms of innate immune-microbial interactions in vocal fold Inflammation (5R01DC012773-09). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10146837. Licensed CC0.

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