Immune system and macrophage activation in the cochlea: Implication for therapeutic intervention

Cochlear inflammation occurs in almost all forms of cochlear disease conditions. This immune activation is mediated by both cellular and molecular components of the cochlear immune system. In the event of inflammatory activation, resident and infiltrating macrophages interact to unleash a cascade of inflammatory mediators. While the precise roles of immune responses in cochlear homeostasis and pathogenesis are not fully understood, anti-inflammatory therapeutics have shown to be beneficial in certain cochlear stress conditions. Recent studies are beginning to reveal the cellular and molecular mechanisms governing inflammatory activities, which in turn offer potential targets for intervention. In this review, we provide an updated overview of the immune anatomy of the cochlea with a focus on the cellular components of the cochlear immune system and macrophage diversity. We describe cochlear inflammatory activities in acute and chronic stress conditions and suggest that controlling the cochlear immune state could offer protection against not only ongoing pathogenesis but also future vulnerability in the event of additional stress. We highlight the potential functional roles of the immune system in cochlear homeostasis and disease, as well as the link between clinical symptoms and cochlear inflammation. Finally, we discuss immune modulations for therapeutic interventions.