Transforming growth factor beta is a major regulator of human neonatal immune responses following respiratory syncytial virus infection

Respiratory syncytial virus (RSV) is a major cause of morbidity and mortality. Previous studies have suggested that T-cell responses may contribute to RSV immunopathology, which could be driven by dendritic cells (DCs). DCs are productively infected by RSV, and during RSV infections, there is an increase of DCs in the lungs with a decrease in the blood. Pediatric populations are particularly susceptible to severe RSV infections; however, DC responses to RSV from pediatric populations have not been examined. In this study, primary isolated DCs from cord blood and adult peripheral blood were compared after RSV infection. Transcriptional profiling and biological network analysis identified transforming growth factor beta (TGF-) and associated signaling molecules as differentially regulated in the two age groups. TGF-1 was decreased in RSV-infected adult-blood DCs but increased in RSV-infected cord blood DCs. Coculture of adult RSV-infected DCs with autologous T cells induced secretion of gamma interferon (IFN-), interleukin 12p70 (IL-12p70), IL-2, and tumor necrosis factor alpha (TNF-). Conversely, coculture of cord RSV-infected DCs and autolo