Natural killer cells attenuate cytomegalovirus-induced hearing loss in mice
Fig 3
Hearing loss in mCMV infected C57BL/6 mice after disruption of NK cell recognition signals.
The effect of Ly49H receptor blockade on hearing loss was evaluated by examining distortion product otoacoustic emission (DPOAE) (A) and auditory brainstem response (ABR) (B) thresholds in post-natal day 28 (4 wks) and post-natal day 42 (6 wks) after intraperitoneal injection of IgG isotype control antibody or Ly49H blocking antibody and/or 200 pfu mCMV-GFP delivered by intracerebral injection on post-natal day 3. Statistically significant threshold differences were seen between the infected mice treated with the IgG isotype control antibody (N = 12 mice) and infected mice treated with the Ly49H blocking antibody 4 weeks post-injection (N = 8 mice) for DPOAE (P < 0.0001) and ABR (P = 0.0001) over the measured tone frequencies. Infected C57BL/6 mice treated with anti-Ly49H antibody and mCMV-GFP showed significant progressive hearing loss at 6 weeks after inoculation compared to thresholds 4 weeks after inoculation (P = 0.001 for DPOAE, P < 0.0001 for ABR). The effect of the mCMV-encoded m157 immunoevasin ligand on hearing loss was tested by comparing DPOAE (C) and ABR (D) in C57BL/6 mice after infection with either a virus deleted for the m157 gene (mCMV Δm157) or its parental wild type virus (mCMV WT1). Statistically significant threshold differences (P < 0.001) were seen between the mCMV WT1 and mCMV Δm157 treated C57BL/6 groups (P < 0.0001 for both DPOAE and ABR). Statistical differences between groups were determined using the Kruskal-Wallis test. ABR and DPOAE thresholds are presented as dB of sound pressure level (dB SPL) as a function of tone frequency in (kHz). Error bars represent standard error of the mean.