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2630220 
Journal Article 
Abstract 
Influenza-A infection alters the immune responsiveness to house dust mite in neonatal mice and accelerates the onset of airway remodeling 
Al-Garawi, A; Walker, T; Fattouh, R; Goncharova, S; Botelho, F; Humbles, AA; Kolbeck, R; Coyle, AJ; Jordana, M 
2010 
Yes 
American Journal of Respiratory and Critical Care Medicine
ISSN: 1073-449X
EISSN: 1535-4970 
181 
A5589 
English 
WOS:000208771003666 
is part of a larger document 3452678 Proceedings of the American Thoracic Society 2010 International Conference, May 14-19, 2010, New Orleans
Rationale: Airway remodeling is a hallmark of chronic allergic airway disease and is thought to contribute to airway dysfunction and, ultimately, clinical symptoms. Epidemiological studies show features of remodeling in children as young as 3 years of age. In addition, early life exposure to respiratory viral infections has been associated with the onset of asthma. However, the precise implications of viral infections on the induction of allergic sensitization, airway inflammation and remodeling during infancy remain to be clarified. We investigated whether an influenza-A infection would alter the allergic immune-inflammatory response to house dust mite (HDM) allergens and accelerate the development of allergic airway remodeling in early life.

Methods: Studies in adult mice (6-8 weeks old) have previously shown that HDM exposure (5 days/week) elicits Th2-type inflammation, including robust eosinophilia, and remodeling after 4-5 weeks of exposure. Here, neonatal mice (8 days old) were infected with influenza-A/PR8/38 virus and 7 days later were exposed to 25µg of HDM (5 days/week) for 3 weeks. Local and systemic immune-inflammatory responses as well as airway remodeling were evaluated 72 hours after the last HDM exposure. Remodeling and airway function were also assessed 3 weeks after the discontinuation of HDM exposure.

Results: We observed that 3 weeks of HDM exposure in neonatal mice elicited a mild immune inflammatory response and no evidence of tissue remodeling. Mice infected with influenza-A at 8 days of age display significant increases in lung dendritic cells as well as acute inflammation. Interestingly, aeroallergen exposure initiated at the time of an acute influenza-A infection elicited a robust inflammatory response comprised of mononuclear cells and eosinophils, that is comparable to that observed in adult mice. This response was associated with increased levels of HDM-specific immunoglobulins (IgE and IgG1) as well as Th1&Th2 cytokines, goblet cell hyperplasia and mucus production. We also detected increased levels of VEGF, TGFβ and PDGF in the BAL along with clear evidence of airway remodeling. Lastly, 3 weeks after cessation of allergen exposure, airway remodeling persisted and was accompanied by the presence of lung dysfunction.

Conclusion: Our data demonstrate that neonatal mice are hyporesponsive to HDM exposure. However, in the context of a flu infection, HDM exposure results in robust allergen-specific immunity, allergic airway inflammation, and the accelerated development of airway remodeling which persists into early adulthood and is associated with reduced lung function. 
American Thoracic Society 2010 International Conference 
New Orleans, LA 
May 14-19, 2010