Natural killer cells attenuate cytomegalovirus-induced hearing loss in mice

PLoS Pathogens

Ali A. Almishaal¹  Wayne M. Yokoyama²  Elaine Hillas²  Pranav D. Mathur³  Yong Wang³  Liting Chen⁴  Anne Zhang⁵  Jun Yang⁵  Matthew A. Firpo⁵  Albert H. Park⁶ 

[1] Department of Communication Sciences and Disorders, University of Utah College of Health, Salt Lake City, Utah, United States of America;Department of Neurobiology and Anatomy, University of Utah School of Medicine, Salt Lake City, Utah, United States of America;Department of Ophthalmology and Visual Sciences, University of Utah School of Medicine, Salt Lake City, Utah, United States of America;Department of Surgery, University of Utah School of Medicine, Salt Lake City, Utah, United States of America;Division of Otolaryngology, University of Utah School of Medicine, Salt Lake City, Utah, United States of America;Division of Rheumatology, Washington University School of Medicine, St. Louis, Missouri, United States of America

关键词: Deafness;    NK cells;    Mouse models;    Outer hair cells;    Cochlea;    Cytomegalovirus infection;    Scanning electron microscopy;    Immune response;   

DOI  :  10.1371/journal.ppat.1006599

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Congenital cytomegalovirus (CMV) infection is the most common non-hereditary cause of sensorineural hearing loss (SNHL) yet the mechanisms of hearing loss remain obscure. Natural Killer (NK) cells play a critical role in regulating murine CMV infection via NK cell recognition of the Ly49H cell surface receptor of the viral-encoded m157 ligand expressed at the infected cell surface. This Ly49H NK receptor/m157 ligand interaction has been found to mediate host resistance to CMV in the spleen, and lung, but is much less effective in the liver, so it is not known if this interaction is important in the context of SNHL. Using a murine model for CMV-induced labyrinthitis, we have demonstrated that the Ly49H/m157 interaction mediates host resistance in the temporal bone. BALB/c mice, which lack functional Ly49H, inoculated with mCMV at post-natal day 3 developed profound hearing loss and significant outer hair cell loss by 28 days of life. In contrast, C57BL/6 mice, competent for the Ly49H/m157 interaction, had minimal hearing loss and attenuated outer hair cell loss with the same mCMV dose. Administration of Ly49H blocking antibody or inoculation with a mCMV viral strain deleted for the m157 gene rendered the previously resistant C57BL/6 mouse strain susceptible to hearing loss to a similar extent as the BALB/c mouse strain indicating a direct role of the Ly49H/m157 interaction in mCMV-dependent hearing loss. Additionally, NK cell recruitment to sites of infection was evident in the temporal bone of inoculated susceptible mouse strains. These results demonstrate participation of NK cells in protection from CMV-induced labyrinthitis and SNHL in mice.

【 授权许可】

CC BY