Research Overview

Our research centers around two of the most common etiologies of respiratory diseases in children: allergic asthma and viral respiratory infections. Our studies are focused on dendritic cells (DCs) and how their function is impacted by these disease entities. DCs comprise a complex system of immune cells uniquely responsible for initiating and directing immune responses. Simply put, they are the “generals” of the immune system army, directing specific responses of such immune system “soldiers” as T cells, B cells, and macrophages. The role of DCs in these clinically relevant disease processes is poorly understood. The projects undergoing investigation in our laboratory are designed to define mechanisms underlying the potential contribution of dendritic cells to the pathogenesis of these diseases.

Asthma, one of the most common diseases affecting children, represents a major focus of our research efforts. Serum IgE, an antibody involved in allergic immune responses, is elevated in patients with allergic asthma. DCs in patients with this disease exhibit increased expression of FcεRI, the high affinity receptor for IgE. Our laboratory recently discovered that plasmacytoid DCs isolated from patients with allergic asthma are impaired in their ability to respond to respiratory viruses compared with those from healthy subjects. In addition, the capacity of plasmacytoid DCs to generate antiviral responses is negatively impacted by activation of this allergic, IgE-mediated pathway. We are currently investigating the mechanisms that govern this apparent counter regulation between FcεRI pathway activation and antiviral responses in human DCs. These findings may explain why asthmatic individuals develop more severe illness when infected with common respiratory viruses.

In another area of investigation, we discovered that DCs are recruited to the respiratory tracts of infants with respiratory viral infections including RSV (Respiratory Syncytial Virus) bronchiolitis and influenza. We have also found that RSV interferes with the expression of MHC Class II on human DCs both in vitro and in patients with RSV infection. This subversion of the DC immune response is associated with a blunted capacity of RSV-exposed DCs to perform one of their critical functions; inducing primary T lymphocyte responses. Failure of RSV-exposed DCs to induce effective T cell responses may underlie the extreme severity of RSV infections in infancy, as well as the recurrence of RSV infection throughout life, findings which have important implications for vaccine development.