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Cochlear Immune Response in Presbyacusis: a Focus on Dysregulation of Macrophage Activity

Abstract

Age-related hearing loss, or presbyacusis, is a prominent chronic degenerative disorder that affects many older people. Based on presbyacusis pathology, the degeneration occurs in both sensory and non-sensory cells, along with changes in the cochlear microenvironment. The progression of age-related neurodegenerative diseases is associated with an altered microenvironment that reflects chronic inflammatory signaling. Under these conditions, resident and recruited immune cells, such as microglia/macrophages, have aberrant activity that contributes to chronic neuroinflammation and neural cell degeneration. Recently, researchers identified and characterized macrophages in human cochleae (including those from older donors). Along with the age-related changes in cochlear macrophages in animal models, these studies revealed that macrophages, an underappreciated group of immune cells, may play a critical role in maintaining the functional integrity of the cochlea. Although several studies deciphered the molecular mechanisms that regulate microglia/macrophage dysfunction in multiple neurodegenerative diseases, limited studies have assessed the mechanisms underlying macrophage dysfunction in aged cochleae. In this review, we highlight the age-related changes in cochlear macrophage activities in mouse and human temporal bones. We focus on how complement dysregulation and the nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 inflammasome could affect macrophage activity in the aged peripheral auditory system. By understanding the molecular mechanisms that underlie these regulatory systems, we may uncover therapeutic strategies to treat presbyacusis and other forms of sensorineural hearing loss.

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Acknowledgements

We thank Jayne Ahlstrom and Crystal Herron for editing the manuscript, Nathaniel Parsons and Abigail McGaha for their comments and help with the references, and Aileen Shi and Rachel Eisenhart for creating the schematics of the complement pathways and NLPR3 inflammasome activation.

Funding

This work was supported by grants from the National Institutes of Health including P50DC000422 (H.L.), SFARI Pilot Award #649452 (H.L.), and K18 DC018517 (H.L.).

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Noble, K., Brown, L., Elvis, P. et al. Cochlear Immune Response in Presbyacusis: a Focus on Dysregulation of Macrophage Activity. JARO (2021). https://doi.org/10.1007/s10162-021-00819-x

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Keywords

  • Presbyacusis
  • Macrophages
  • Stria vascularis
  • Auditory nerve
  • Complement system
  • NLRP3 inflammasome