Cleaved Cochlin Sequesters Pseudomonas aeruginosa and Activates Innate Immunity in the Inner Ear

裂解的 Cochlin 隔离铜绿假单胞菌并激活内耳的先天免疫

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作者:Jinsei Jung, Jee Eun Yoo, Young Ho Choe, Sang Chul Park, Hyun Jae Lee, Hack June Lee, Byunghwa Noh, Sung Huhn Kim, Gyeong-Yi Kang, Kang-Mu Lee, Sang Sun Yoon, Dong Su Jang, Joo-Heon Yoon, Young-Min Hyun, Jae Young Choi

Abstract

In the inner ear, endolymph fluid surrounds the organ of Corti, which is important for auditory function; notably, 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 Pseudomonas aeruginosa infection in the cochlea. Upon infection, the LCCL domain is cleaved from cochlin and secreted into the perilymph. This cleaved fragment sequesters infiltrating bacteria in the scala tympani and subsequently recruits resident immune cells to eliminate the bacteria. Importantly, hearing loss in a cochlin knockout mouse model is remedied by treatment with a cochlin LCCL peptide. These findings suggest cleaved cochlin LCCL constitutes a critical factor in innate immunity and auditory function and may be a potential therapeutic target to treat chronic otitis media-induced hearing loss.

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