# The role of resident tissue macrophages in cytomegalovirus-associated sensorineural hearing loss

> **NIH NIH F31** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2024 · $47,169

## Abstract

ABSTRACT
The cochlea is a delicate and structurally complex part of the inner ear peripheral auditory system that is
developmentally sensitive to early life infection and inflammation. Recent studies have shown fetal-derived
resident tissue macrophages (RTMs) are distributed across key areas of the cochlea, and are required for proper
cochlea development. Our preliminary data and published data identify cochlea RTMs as sensitive responders
to cytomegalovirus (CMV) and are implicated in cochlear damage and sensorineural hearing loss (SNHL). While
fetal-derived RTMs have been identified in cochlea, their precise origin and function is unknown. RTMs are
heterogeneous and include 1) primitive macrophages derived from yolk sac hematopoiesis and 2) definitive
macrophages derived from fetal liver hematopoiesis. We will investigate relative contribution of primitive and
definitive RTMs in normal cochlea development, their spatial distribution within the cochlea, and examine how
these interactions go awry in response to CMV infection to drive dysfunction. Our investigation offers a unique
opportunity to understand both how tissue environment can influence phenotype and how spatial seeding of
RTMs influences normal tissue development and architecture. Our working hypothesis is that CMV infection
drives abnormal cochlea RTM development, thereby impairing cochlea tissue development and causing SNHL.
We will investigate this hypothesis by completing our following aims:
 Aim 1: Determine the origin, localization, and contribution of specific RTM subsets within the cochlea
 Aim 2: Understand the role of specific RTM subsets in cochlear tissue development and function
 Aim 3: Determine the impact of CMV on the establishment and persistence of fetal-derived RTMs
The objective of this proposed work is to elucidate new level of mechanistic insight into how RTMs contribute to
normal function of cochlea tissue and cochlear immunity, and within the context of disease and disorders, how
RTMs mediate CMV-associated SNHL. This proposal will shed light on pathological mechanisms of SNHL on
RTM and cochlea tissue. Collectively the proposed work will, for the first time, give us insight into the link between
fetal-derived resident cells and tissue architecture, and will provide insight for RTMs as a potential novel
therapeutic target for SNHL treatment.

## Key facts

- **NIH application ID:** 10930030
- **Project number:** 5F31DC021388-02
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Kelly Otsuka
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $47,169
- **Award type:** 5
- **Project period:** 2023-09-30 → 2025-09-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10930030

## Citation

> US National Institutes of Health, RePORTER application 10930030, The role of resident tissue macrophages in cytomegalovirus-associated sensorineural hearing loss (5F31DC021388-02). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10930030. Licensed CC0.

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