Figure 10.

Hypothetical representation of the immune interaction between the endolymphatic sac (ES) and the inner ear in man. The ES receives antigens and waste material via the endolymphatic duct, which activates resident macrophages/monocytes that then migrate into the sac lumen. After phagocytosis, cells migrate back into the perisaccular tissue for antigen presentation and immune processing. MHC class II molecules, reinforced by TLR4, and under IFNγ stimuli, bind to endocytosed, and degraded peptides within the cytoplasm and transport the peptides to the cell membrane for presentation to CD4+ T cells. The lymphocytes recirculate into the bloodstream to “prime” the inner ear cells. The immune activation of the inner ear is located “off-site” to avoid pro-inflammatory activation near the vulnerable hair cells. The chemokine fractalkine assists in attracting macrophages to the ES (2, 4, 5, 10, 17).