Severe respiratory viral infections early in childhood are associated with a markedly increased risk of asthma. Using the Sendai virus (SeV) mouse model, we defined a mechanistic pathway translating viral infection into asthma. Critical to the development of post-viral asthma is the formation of anti-viral IgE. Since IgE binds mast cells and basophils, it would seem that they may play a role in the anti-viral immune response, but this had not been previously tested. We hypothesized that via IgE mast cells would be required for the development of asthma after a severe respiratory viral infection.
Wild-type (WT) and KitW-sh (mast cell deficient) mice (n=3-4) were inoculated with SeV. On day 21 post-inoculation SeV, airway hyper-responsiveness (AHR) was measured with non-invasive two-chamber plethysmography. Lungs were homogenized and levels of mucous (Muc5ac) as well as Il13 message were measured using quantitative, reverse-transcript PCR and compared to Gapdh levels. Student’s t-test was used in data analysis.
WT and KitW-sh mice survived the viral infection, and developed airway hyperreactivity and mucous cell metaplasia. Interestingly, airway hyperreactivity was significantly greater in the mast cell deficient mice (p=0.05 versus WT), while Muc5ac and Il13 were not different between the two groups.
Our data suggest that mast cells are not required for survival from a respiratory viral infection, and may even attenuate development of post-viral airway hyper-reactivity. Confirmation of the role of mast cells awaits mast cell reconstitution studies in mast cell deficient mice, something that we are currently undertaking.