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

Abstract

Objective: Our objective was to determine whether the receptor CX3CR1 is necessary for the recruitment of macrophages to the cochlea in chronic suppurative otitis media (CSOM) and if its deletion can prevent hair cell loss in CSOM. Background: CSOM is a neglected disease that afflicts 330 million people worldwide and is the most common cause of permanent hearing loss among children in the developing world. It is characterized by a chronically discharging infected middle ear. We have previously demonstrated that CSOM causes macrophage associated sensory hearing loss. The receptor CX3CR1 is expressed on macrophages, which have been shown to be increased at the time point of outer hair cell (OHC) loss in CSOM. Methods: In this report, we examine the influence of CX3CR1 deletion (CX3CR1 −/− ) in a validated model of Pseudomonas aeruginosa (PA) CSOM. Results: The data show no difference in OHC loss between the CX3CR1 −/− CSOM group and CX3CR1 +/+ CSOM group ( p = 0.28).We observed partial OHC loss in the cochlear basal turn, no OHC loss in the middle and apical turns in both CX3CR1 −/− and CX3CR1 +/+ CSOM mice at 14 days after bacterial inoculation. No inner hair cell (IHC) loss was found in all cochlear turns in all groups. We also counted F4/80 labeled macrophages in the spiral ganglion, spiral ligament, stria vascularis and spiral limbus of the basal, middle, and apical turn in cryosections. We did not find a significant difference in the total number of cochlear macrophages between CX3CR1 −/− mice and CX3CR1 +/+ mice ( p = 0.97). Conclusion:The data did not support a role for CX3CR1 macrophage associated HC loss in CSOM.