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.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1016/j.chom.2019.02.001 | DOI Listing |
Hear Res
December 2021
Department of Otorhinolaryngology, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, Republic of Korea. Electronic address:
Unlabelled: Acoustic trauma induces an inflammatory response in the cochlea, resulting in debilitating hearing function. Clinically, amelioration of inflammation substantially prevents noise-induced hearing loss. The Limulus factor C, Cochlin, and Lgl1 (LCCL) peptide plays an important role in innate immunity during bacteria-induced inflammation in the cochlea.
View Article and Find Full Text PDFBMB Rep
September 2020
Departments ofAnatomy, Yonsei University College of Medicine, Seoul 03722; BK21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Korea.
The inner ear is a complex and delicate structure composed of the cochlea and the vestibular system. To maintain normal auditory function, strict homeostasis of the inner ear is needed. A proper immune response against infection, thus, is crucial.
View Article and Find Full Text PDFCell Host Microbe
April 2019
Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, 100 Piedmont Avenue SE, Atlanta, GA 30303, USA. Electronic address:
Since the inner ear is an important but sensitive organ of hearing, bacteria-driven immune responses must be tightly controlled. In this issue of Cell Host & Microbe, Jung et al. (2019) demonstrate that cleaved cochlin plays a dual role to trap bacteria and recruit immune cells to improve ear function.
View Article and Find Full Text PDFCell Host Microbe
April 2019
Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, South Korea; Airway Mucus Institute, Yonsei University College of Medicine, Seoul, South Korea. Electronic address:
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.
View Article and Find Full Text PDFHum Mutat
December 2015
Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, Republic of Korea.
DFNA9 is an autosomal dominant disorder characterized by late-onset, non-syndromic hearing loss, and vestibular dysfunction. Mutations in the COCH (coagulation factor C homology) gene encoding cochlin are etiologically linked to DFNA9. Previous studies have shown that cochlin is cleaved by aggrecanase-1 during inflammation in the spleen and that the cleaved LCCL domain functions as an innate immune mediator.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!