Respiratory syncytial virus (RSV) is the single-most important pathogen for severe lower respiratory tract infection in infants and young children worldwide, and RSV-induced bronchiolitis in early childhood is strongly linked to the subsequent development of allergy and asthma. However, the regulation of the immune responses to RSV infection, or the early immune mechanisms of RSV pathogenesis, is unknown. Current evidence suggests that RSV-, but not influenza A virus (IFZ)-, induced severe bronchiolitis is associated with a Th2 predominant immune response or a decreased Th1 immune response, indicating that RSV may have unique characteristics in modulating immune responses in susceptible subjects. Our laboratory has described the immune responses to RSV infection in a mouse model, in which it was shown that RSV can induce a strong Th2 immune response in BALB/c mice. The proposed studies will have the following two specific aims: (1) to define and characterize the different immune responses, inflammatory responses, and airway hyperreactivity (AHR) to RSV and IFZ infections in BALB/c mice with C57BL/6 mice as controls; (2) to determine whether the divergent immune and inflammatory responses in BALB/c and C57BL/6 mice induced by RSV and IFZ infections are driven by different functional states of lung dendritic cells (DCs). The proposed experiments seek to improve our understanding of the regulation of immune responses to RSV infection by lung DCs. Specifically, with the BALB/c and C57BL/6 mouse models of virus infection, the proposed studies will determine: (1) if RSV infection induces a strong Th2 immune response with enhanced inflammatory response and AHR, which is distinct from that induced by IFZ; (2) whether the Th2 immune response induced by RSV infection is driven by lung DCs. In the long term, these studies will improve our understanding of the immune regulation and the pathogenesis of RSV infection, and may lead to novel therapies for RSV-induced airway disease. ? ?
| Senft, Albert P; Taylor, Reed H; Lei, Wanli et al. (2010) Respiratory syncytial virus impairs macrophage IFN-alpha/beta- and IFN-gamma-stimulated transcription by distinct mechanisms. Am J Respir Cell Mol Biol 42:404-14 |
