Respiratory syncytial virus (RSV) is the leading respiratory pathogen in infants and young children worldwide. RSV infection does not induce protective immunity and therefore repeated RSV infections occur throughout life. In addition to the considerable morbidity caused by acute RSV infections, numerous studies have described a strong association between RSV bronchiolitis in infancy and abnormal pulmonary function later in life. Exaggeration of the immune response to RSV infection is thought to play a significant role in the development of these long-term pulmonary abnormalities. Despite decades of research, however, our understanding of the immune responses induced by RSV remains limited. The goal of this proposal is to investigate the effect of RSV on the immune system in the context of human dendritic cells (DCs), since these cells are uniquely capable of inducing primary immune responses and thus bridge the innate and adaptive immune systems. The central hypothesis of this project is that RSV skews immune responses toward Type 2 inflammatory responses via targeting plasmacytoid DCs. The studies proposed herein will begin to define the mechanisms involved in the interaction between RSV and DCs and how these interactions influence the establishment of T cell responses. We believe that these studies may ultimately contribute to the development of immunomodulatory strategies aimed at prevention of RSV infection. The immediate goal of the candidate is to procure further training in basic science investigation to enhance her research skills and allow her to develop a career as an independent investigator. As a career focus, the candidate plans to concentrate on the immunopathogenesis of the host/viral pathogen relationship with an emphasis on the role of DCs in this relationship. To assist in achieving this goal, the research proposal calls for the attainment of new scientific technical and intellectual skills while concurrently investigating a timely research project, the alterations of human dendritic cell subsets by RSV. Both the University of Texas Southwestern Medical Center and the Baylor Institute for Immunology Research provide fertile laboratory environments in terms of available laboratory facilities/equipment and experienced, successful faculty members committed to mentoring the candidate. This award will facilitate the transition of the candidate into an independent, academic physician scientist.
| Huber, Jonathan P; Ramos, Hilario J; Gill, Michelle A et al. (2010) Cutting edge: Type I IFN reverses human Th2 commitment and stability by suppressing GATA3. J Immunol 185:813-7 |
| Gill, Michelle A; Bajwa, Gagan; George, Tiffany A et al. (2010) Counterregulation between the FcepsilonRI pathway and antiviral responses in human plasmacytoid dendritic cells. J Immunol 184:5999-6006 |
| Gill, Michelle A; Long, Kristin; Kwon, Theresa et al. (2008) Differential recruitment of dendritic cells and monocytes to respiratory mucosal sites in children with influenza virus or respiratory syncytial virus infection. J Infect Dis 198:1667-76 |
