Pertussis toxin sensitization alters the pathogenesis of subsequent respiratory syncytial virus infection

Evidence suggests that both host and viral factors influence disease severi ty after infection with respiratory syncytial virus (RSV), To characterize the effects of pertussis toxin (PT) sensitization on subsequent RSV infecti on, BALB/c mice were treated with PT parenterally before RSV challenge. Pri ming with purified and detoxified PT before RSV challenge increased postcha llenge weight loss and mortality. PT priming changed the kinetics, location , and composition of the cellular infiltrate in the lung but altered neithe r antibody responses nor virus titers, Passive transfer of PT-sensitized sp lenocytes produced similar responses. Priming with purified, but not geneti cally detoxified, PT propagated a modest type 2 cytokine response to RSV an tigens. However, anti-interleukin-4 treatment before RSV challenge failed t o abrogate the effects of PT priming, These data confirm that the preexisti ng immune environment can change virus-specific immunity and provide both a model for study of RSV disease and evidence that noninfectious immunomodul ators may impact pathogen-specific immunity.