Murine Cytomegalovirus Influences Foxj1 Expression, Ciliogenesis, and Mucus Plugging in Mice with Allergic Airway Disease

Carol A. Wu^*, John J. Peluso, John D. Shanley, Lynn Puddington^* and Roger S. Thrall^*

From the Departments of Immunology,^*Cell Biology,and Medicine,University of Connecticut Health Center, Farmington, Connecticut

We have followed throughout time the development of allergicairway disease (AAD) in both uninfected mice and mice infectedintranasally with murine cytomegalovirus (MCMV). Histologicalevaluation of lung tissue from uninfected mice with AAD demonstratedmucus plugging after 14 and 21 days of ovalbumin-aerosol challenge,with resolution of mucus plugging occurring by 42 days. In MCMV/AADmice, mucus plugging was observed after 7 days of ovalbumin-aerosolchallenge and remained present at 42 days. The level of interleukin-13in bronchoalveolar lavage fluid from MCMV/AAD mice was decreasedcompared with AAD mice and was accompanied by increased levelsof interferon- ${gamma}$ . Levels of Muc5A/C, Muc5B, or Muc2 mucin mRNAin the lungs of MCMV/AAD mice were not elevated compared withAAD mice. MCMV was able to infect the airway epithelium, resultingin decreased expression of Foxj1, a transcription factor criticalfor ciliogenesis, and a loss of ciliated epithelial cells. Inaddition, an increase in the number of epithelial cells stainingpositive for periodic acid-Schiff was observed in MCMV/AAD airways.Together, these findings suggest that MCMV infection of theairway epithelium enhances goblet cell metaplasia and diminishesefficient mucociliary clearance in mice with AAD, resultingin increased mucus plugging.