Deciphering Mechanisms Linking Childhood Viral Infection and Asthma Development

Key Words: Macrophages, Repair, Influenza, Tissue remodeling, Inflammation, Asthma

Asthma is the most common chronic medical condition in children, affecting up to 10% of pediatric and adolescent populations. Viral infection early in life is thought to predispose these populations to the development of asthma, however the mechanisms explaining this association are not fully understood. Respiratory infections induce robust immune responses to clear pathogens, resulting in collateral damage to the airways. Rapid repair is thus required to preserve respiratory function and promote survival. We predict that viral infection results in long-term remodeling of the airway which may drive subsequent asthma development. We will utilize a juvenile mouse model of influenza infection and focus our analyses on the trachea. The murine trachea most closely represents human intrapulmonary airways—the site of asthmatic pathology—and thus serves as the ideal tissue for our studies. In addition to the inner tracheal surface, surrounding structural cells, and smooth muscle, the trachea is home to immune cell populations, including macrophages. This immune cell type is crucial for antiviral defense and repair of tissue damage. Therefore, we hypothesize that macrophages contribute to the repair, remodeling, and reprogramming that occurs in the airway following viral infection. Our proposed work will elucidate the repair and remodeling pathways that follow viral infection and determine how these mechanisms predispose children to later development of asthma.

Currently, treatments only target the symptoms of asthma, not the underlying drivers of disease. We are motivated by this line of research because mechanistic understanding of acute and long-term responses to viral infection is lacking. Comprehensive knowledge of airway repair and remodeling will help clarify the association between early life viral infection and the development and exacerbation of asthma. Furthermore, these findings may provide therapeutic strategies to prevent or cure asthma and other wheezing diseases in children.