Cleaved Cochlin Sequesters Pseudomonas Aeruginosa and Activates Immunity in the Inner Ear

Abstract

In the inner ear, endolymph fluid surrounds the organ of Corti, which is important for auditory function, and even slight environmental changes mediated by trauma or infection can have significant consequences. However, it is unclear how the immune response is modulated in these tissues. Here, we report the local immune-surveillance role of cleaved cochlin LCCL (Limulus factor C, Cochlin, and Lgl1) during pseudomonal infection in the cochlea. Upon infection, the LCCL domain is cleaved from cochlin and secreted into the perilymph space. This cleaved fragment then induced bacterial aggregation in the scala tympani and subsequently recruited resident immune cells to eliminate the bacteria. Importantly, hearing loss in a cochlin knock-out mouse model was remedied by treatment with cochlin LCCL. These findings suggest that cleaved cochlin LCCL is a critical factor in innate immunity and auditory function and could be a potential therapeutic target to treat chronic otitis media-induced hearing loss.