title: Pertussis toxin sensitization alters the pathogenesis of subsequent respiratory syncytial virus infection.
abstract: Evidence suggests that both host and viral factors influence disease severity after infection with respiratory syncytial virus (RSV). To characterize the effects of pertussis toxin (PT) sensitization on subsequent RSV infection, BALB/c mice were treated with PT parenterally before RSV challenge. Priming with purified and detoxified PT before RSV challenge increased postchallenge weight loss and mortality. PT priming changed the kinetics, location, and composition of the cellular infiltrate in the lung but altered neither antibody responses nor virus titers. Passive transfer of PT-sensitized splenocytes produced similar responses. Priming with purified, but not genetically detoxified, PT propagated a modest type 2 cytokine response to RSV antigens. However, anti-interleukin-4 treatment before RSV challenge failed to abrogate the effects of PT priming. These data confirm that the preexisting immune environment can change virus-specific immunity and provide both a model for study of RSV disease and evidence that noninfectious immunomodulators may impact pathogen-specific immunity.
authors.affiliation: Department of Microbiology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2582, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Fischer
authors.forename: J E
authors.initials: JE
authors.lastname: Johnson
authors.forename: T R
authors.initials: TR
authors.lastname: Johnson
authors.forename: B S
authors.initials: BS
authors.lastname: Graham
mesh_terms: D000818:Animals; D015721:Diphtheria-Tetanus-Pertussis Vaccine / Q000494:pharmacology*; D018450:Disease Progression; D005260:Female; D007116:Immunization, Passive; D015847:Interleukin-4 / Q000494:pharmacology; D017710:Lymphocyte Transfusion; D051379:Mice; D008807:Mice, Inbred BALB C; D037342:Pertussis Toxin; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology*; D012136:Respiratory Syncytial Viruses / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D013154:Spleen / Q000276:immunology; D013997:Time Factors; D010948:Viral Plaque Assay; D010566:Virulence Factors, Bordetella / Q000276:immunology / Q000494:pharmacology*; D015431:Weight Loss / Q000187:drug effects
chemical_list: D015721:Diphtheria-Tetanus-Pertussis Vaccine; D010566:Virulence Factors, Bordetella; D015847:Interleukin-4; D037342:Pertussis Toxin