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Published on: October 29, 2018
The Time Course of Monocytes Infiltration After Acoustic Overstimulation
Seung Ho Shin1, Jinsei Jung2,3, Haeng Ran Park2
1Department of Otorhinolaryngology-Head and Neck Surgery, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin, South Korea.
Abstract:
Cochlea macrophages regulate cochlea inflammation and may harbors the potentials to protect hearing function from injury, including acoustic overstimulation. Cochlea macrophage numbers increase at 3-7 days after acoustic stimulation. However, the exact timing of macrophage infiltration and maturation from inflammatory monocytes is unclear. Furthermore, neutrophils may also be involved in this process. Therefore, in this study, we investigated time-dependent immune cell infiltration, macrophage transformation, and neutrophil involvement following acoustic stimulation. Flow cytometry and immunofluorescence were conducted in C-X3-C motif chemokine receptor 1 (CX3CR1)+/GFP mice after acoustic overstimulation (at baseline and at 1, 2, 3, and 5 days after exposure to 120 dB for 1 h) to identify inflammatory monocytes in the cochlea. RNA-sequencing and quantitative polymerase chain reaction were performed to identify differentially expressed genes. Inflammatory monocytes infiltrated into the lower portion of the lateral wall within 2 days after acoustic overstimulation (dpn), followed by transformation into macrophages at 3-5 dpn via CX3CR1 upregulation and Ly6C downregulation. In addition, inflammatory monocytes were aggregated inside the collecting venule only at 1 dpn. Neutrophils were not a major type of phagocyte during this response. The gene encoding C-C motif chemokine ligand 2 gene was significantly upregulated as early as 3 h after acoustic overstimulation. Given these results, treatment to control immune response after a noise-induced hearing loss should be applied as soon as possible.
Insights
Cochlea macrophages protect hearing after noise injury. Inflammatory monocytes infiltrate within 2 days, transforming into macrophages by 3-5 days post-stimulation, indicating early immune intervention is crucial for noise-induced hearing loss.
Area of Science:
- Neuroscience
- Immunology
- Otolaryngology
Background:
- Cochlea macrophages modulate inflammation and hearing protection against acoustic overstimulation.
- Macrophage numbers increase 3-7 days post-acoustic stimulation, but infiltration timing is unclear.
- Neutrophil involvement in cochlear immune response to noise is also uncertain.
Purpose of the Study:
- To investigate the time-dependent infiltration and transformation of immune cells, particularly macrophages, following acoustic overstimulation.
- To clarify the role of inflammatory monocytes and neutrophils in the cochlear response to noise.
- To identify key molecular events and gene expression changes during this process.
Main Methods:
- Utilized CX3CR1+/GFP mice exposed to acoustic overstimulation (120 dB for 1 h).
- Employed flow cytometry and immunofluorescence to track immune cell infiltration and transformation.
- Conducted RNA-sequencing and quantitative PCR to analyze gene expression changes at various time points (baseline, 1, 2, 3, 5 days post-stimulation).
Main Results:
- Inflammatory monocytes infiltrated the cochlea's lateral wall within 2 days post-acoustic overstimulation (dpn).
- These monocytes transformed into macrophages between 3-5 dpn, characterized by increased CX3CR1 and decreased Ly6C expression.
- Neutrophils were not primary phagocytes; C-C motif chemokine ligand 2 gene was upregulated as early as 3 hours post-stimulation.
Conclusions:
- Immune response in the cochlea following acoustic overstimulation involves rapid infiltration and transformation of monocytes into macrophages.
- Early intervention targeting immune responses is critical for managing noise-induced hearing loss.
- Understanding the kinetics of immune cell dynamics provides therapeutic targets for hearing protection.

