The Role of Stromal Cells in the Immune Response to Respiratory Syncytial Virus (RSV) Infection In Vivo

The characteristics of RSV infection and spread in the lung are not well defined. In vitro studies have shown stromal cells, especially epithelial cells, to express inflammatory mediators, however their importance to the cytokine and chemokine production in vivo during RSV infection has not been established. We have been able to identify several important chemokines, cytokines and growth factors that are expressed by stromal cells in response to RSV in vivo using fluorescent activated cell sorting and gene expression analysis, as well as via intracellular cytokine staining. Interestingly, our data show that alveolar type II epithelial cells are the main producers of growth factors while the non-epithelial, non-endothelial stromal cells are the main source of chemokines. In addition, neutralisation experiments of one of these growth factors, granulocyte macrophage colony-stimulating factor (GM-CSF) in vivo, influence lung inflammation, suggesting this it is important for regulating cellular responses and viral clearance. Data from these experiments will highlight a novel and previously unknown role of stromal cells in the immune response to RSV infection in vivo and go towards future development of therapeutics and vaccines.