Virus-specific IgE Enhances Airway Responsiveness on Reinfection with Respiratory Syncytial Virus in Newborn Mice

Background: Respiratory syncytial virus (RSV)-specific IgE is a component of the host response to RSV infection, but its role in the subsequent enhancement of altered airway responsiveness is unknown.

Objective: To define the role of RSV-specific IgE in the enhancement of airway responsiveness on reinfection of newborn mice.

Methods: Mice were infected as newborns with RSV and were reinfected 5 weeks later. The role of IgE was determined by documenting RSV-specific IgE response after neonatal infection, and by assessing airway responsiveness on reinfection.

Results: After neonatal infection, wild-type (WT) mice developed an RSV-specific IgE response. On reinfection, these mice developed enhanced airway hyperresponsiveness (AHR), airway eosinophilia, and mucus hyperproduction, and their T-cell cytokine response was skewed toward a T(H)2 phenotype. None of these altered responses developed on reinfection of IL-4(-/-)/IL-13(-/-) mice, and no RSV-specific IgE could be detected after neonatal infection of these mice. Fc epsilon RI(-/-) mice did not develop the enhanced AHR on reinfection, and airway eosinophilia and mucus production were significantly attenuated. These responses could be restored in deficient mice reconstituted with WT mast cells. In RSV-infected newborn WT mice, administration of anti-IgE prevented the enhancement of AHR and attenuated eosinophilia and mucus hyperproduction on reinfection, an effect that was associated with diminished T(H)2 cytokine production and increased IFN-gamma production.

Conclusion: Respiratory syncytial virus-specific IgE enhances the development of T(H)2-biased airway responsiveness on reinfection of mice initially infected as newborns.