Editors' ChoiceHost-Pathogen Interactions

Protecting the organ of Corti from damage

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Science Signaling  07 May 2019:
Vol. 12, Issue 580, eaax8884
DOI: 10.1126/scisignal.aax8884

The LCCL domain of cochlin protects hearing by sequestering bacterial pathogens and stimulating innate immune responses.

Infections, ototoxic drugs, and excessively loud sounds can damage the organ of Corti in the cochlea, leading to hearing loss. Because the organ is not accessible to systemic immune cells, local innate immune responses protect it from infection-induced damage. Cochlin, a protein that contains a Limulus factor C, cochlin, and Lgl1 (LCCL) domain and two von Willebrand factor A (vWFA)–like domains that mediate interaction with the extracellular matrix, is abundant in the inner ear and is required for the maintenance of hearing. Jung et al. report that infection of the mouse inner ear with Pseudomonas aeruginosa stimulated the release of the cochlin LCCL domain into the cochlear fluid (perilymph) in a manner that depended on the extracellular metalloprotease aggrecanase 1. Injection of the LCCL domain into the inner ear protected Cochlin−/− mice from infection-induced hearing loss. The release of the LCCL domain was required for the infection-stimulated production of the inflammatory cytokines interleukin-1β (IL-1β) and IL-6 in the cochlea and for the recruitment of macrophages and neutrophils to the scala tympani, the perilymph-filled cavity adjacent to the organ of Corti. In vitro, the cochlin LCCL domain bound to and induced the aggregation of P. aeruginosa and several other ear infection–causing bacterial species and acted as a chemoattractant for neutrophils. In infected mice, it prevented bacteria from spreading throughout the cochlea, restricting them to the scala tympani. These findings demonstrate that cochlin plays a dual role in protecting the organ of Corti from infection-induced damage by both sequestering bacteria and promoting innate immune responses. Determining what triggers the cleavage of cochlin and how it interacts with both bacteria and innate immune cells will be important for any proposed strategies exploiting this system to treat hearing loss (see also commentary by Komatsu and Li).

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