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Chemokine Receptor CCR2 Is Protective toward Outer Hair Cells in Chronic Suppurative Otitis Media
Ankur Gupta1, Viktoria Schiel1, Ritwija Bhattacharya1
1Department of Otolaryngology - Head and Neck Surgery, School of Medicine, Stanford University, Palo Alto, CA.
Abstract:
Chronic suppurative otitis media (CSOM) is a neglected disease that afflicts 330 million people worldwide and is the most common cause of permanent hearing loss among children in the developing world. Previously, we discovered that outer hair cell (OHC) loss occurred in the basal turn of the cochlea and that macrophages are the major immune cells associated with OHC loss in CSOM. Macrophage-associated cytokines are upregulated. Specifically, CCL-2, an important member of the MCP family, is elevated over time following middle ear infection. CCR2 is a common receptor of the MCP family and the unique receptor of CCL2. CCR2 knockout mice (CCR2-/-) have been used extensively in studies of monocyte activation in neurodegenerative diseases. In the present study, we investigated the effect of CCR2 deletion on the cochlear immune response and OHC survival in CSOM. The OHC survival rate was 84 ± 12.5% in the basal turn of CCR2+/+ CSOM cochleae, compared with was 63 ± 19.9% in the basal turn of CCR2-/- CSOM cochleae (p ≤ 0.05). Macrophage numbers were significantly reduced in CCR2-/- CSOM cochleae compared with CCR2+/+ CSOM cochleae (p ≤ 0.001). In addition, CCL7 was upregulated, whereas IL-33 was downregulated, in CCR2-/- CSOM cochleae. Finally, the permeability of the blood-labyrinth barrier in the stria vascularis remained unchanged in CCR2-/- CSOM compared with CCR2+/+ CSOM. Taken together, the data suggest that CCR2 plays a protective role through cochlear macrophages in the CSOM cochlea.
Insights
CCR2 deletion worsens outer hair cell loss in chronic suppurative otitis media (CSOM) by altering cochlear macrophage activity. This suggests CCR2 plays a protective role in CSOM-related hearing loss.
Area of Science:
- Immunology
- Otolaryngology
- Neuroscience
Background:
- Chronic suppurative otitis media (CSOM) is a major cause of childhood hearing loss.
- Outer hair cell (OHC) loss and macrophage infiltration are key features of CSOM.
- CCL2/CCR2 signaling is implicated in inflammatory responses.
Purpose of the Study:
- To investigate the role of CCR2 in the cochlear immune response and OHC survival in a mouse model of CSOM.
Main Methods:
- Utilized CCR2 knockout (CCR2-/-) and wild-type (CCR2+/+) mice with induced CSOM.
- Assessed OHC survival rates in the cochlear basal turn.
- Quantified macrophage infiltration.
- Analyzed cytokine expression (CCL7, IL-33).
- Evaluated blood-labyrinth barrier permeability.
Main Results:
- CCR2 deletion significantly reduced OHC survival in CSOM cochleae.
- Macrophage numbers were significantly lower in CCR2-/- CSOM cochleae.
- CCL7 was upregulated, and IL-33 was downregulated in CCR2-/- CSOM cochleae.
- Blood-labyrinth barrier permeability remained unchanged.
Conclusions:
- CCR2 signaling, mediated by cochlear macrophages, plays a protective role in preserving OHCs during CSOM.
- Targeting the CCR2 pathway may offer therapeutic potential for preventing hearing loss in CSOM.
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