Chronic suppurative otitis media causes macrophage-associated sensorineural hearing loss

Abstract

Background Chronic suppurative otitis media (CSOM) is the most common cause of permanent hearing loss in children in the developing world. A large component of the permanent hearing loss is sensory in nature and our understanding of the mechanism of this has so far been limited to post-mortem human specimens or acute infection models that are not representative of human CSOM. In this report, we assess cochlear injury in a validated Pseudomonas aeruginosa (PA) CSOM mouse model. Methods We generated persisters (PCs) and inoculated them into the mouse middle ear cavity. We tracked infection with IVIS and detected PA using RT-PCR. We assessed cochlear damage and innate immunity by Immunohistochemistry. Finally, we evaluated cytokines with multiplex assay and quantitative real-time PCR. Results We observed outer hair cell (OHC) loss predominantly in the basal turn of the cochlear at 14 days after bacterial inoculation. Macrophages, not neutrophils are the major immune cells in the cochlea in CSOM displaying increased numbers and a distribution correlated with the observed cochlear injury. The progression of the morphological changes suggests a transition from monocytes into tissue macrophages following infection. We also show that PA do not enter the cochlea and live bacteria are required for cochlear injury. We characterized cytokine activity in the CSOM cochlea. Conclusions Taken together, this data shows a critical role for macrophages in CSOM-mediated sensorineural hearing loss (SNHL).

Influence of CX3CR1 Deletion on Cochlear Hair Cell Survival and Macrophage Expression in Chronic Suppurative Otitis Media

“…We have previously shown that macrophages are the main immune cells present in the cochlea at the timepoint of OHC loss and found elevated levels of proinflammatory cytokines, which are known to be produced by activated macrophages. We also found that direct bacterial invasion is not the cause of hair cell injury in CSOM (12). These findings show a potential role of macrophages toward SHL in CSOM.…”

“…In CSOM, we have previously observed a significant increase of cochlear macrophages around the timepoint of hair cell death at 14 days after the infection, suggesting their recruitment to the cochlea (12). In the current study, we tested whether CX3CR1 is necessary for macrophage recruitment to the cochlea and whether the receptor depletion could potentially prevent OHC loss.…”

“…In this model, we documented the timing of the hearing loss and found that PA did not enter the inner ear and therefore were unlikely to directly cause SHL. We documented macrophage recruitment in direct association with the observed timing and pattern of SHL (12). We do not yet know if these macrophages are reacting to, or causing, hair cell (HC) injury in CSOM.…”

“…We previously showed that SHL in CSOM is associated with macrophages, and that direct bacterial invasion or direct ototoxin exposure are not the source for hair cell injury (12). There is an accumulation of macrophages in the cochlea at the timepoint of OHC loss.…”

Anti-inflammatory properties and characterization of water extracts obtained from Callicarpa kwangtungensis Chun using in vitro and in vivo rat models

“…In inflammatory responses, activated macrophages release large amounts of cytokines, further increasing inflammatory responses 40 . NO, TNF-α and IL-6 are produced in acute and chronic inflammatory diseases 41 .…”