title: Dual proinflammatory and antiviral properties of pulmonary eosinophils in respiratory syncytial virus vaccine-enhanced disease.
abstract: Human respiratory syncytial virus (RSV) is a major cause of morbidity and severe lower respiratory tract disease in the elderly and very young, with some infants developing bronchiolitis, recurrent wheezing, and asthma following infection. Previous studies in humans and animal models have shown that vaccination with formalin-inactivated RSV (FI-RSV) leads to prominent airway eosinophilic inflammation following RSV challenge; however, the roles of pulmonary eosinophilia in the antiviral response and in disease pathogenesis are inadequately understood. In vivo studies in mice with eotaxin and/or interleukin 5 (IL-5) deficiency showed that FI-RSV vaccination did not lead to enhanced pulmonary disease, where following challenge there were reduced pulmonary eosinophilia, inflammation, Th2-type cytokine responses, and altered chemokine (TARC and CCL17) responses. In contrast to wild-type mice, RSV was recovered at high titers from the lungs of eotaxin- and/or IL-5-deficient mice. Adoptive transfer of eosinophils to FI-RSV-immunized eotaxin- and IL-5-deficient (double-deficient) mice challenged with RSV was associated with potent viral clearance that was mediated at least partly through nitric oxide. These studies show that pulmonary eosinophilia has dual outcomes: one linked to RSV-induced airway inflammation and pulmonary pathology and one with innate features that contribute to a reduction in the viral load.
  
  
  OBJECTIVE
  This study is critical to understanding the mechanisms attributable to RSV vaccine-enhanced disease. This study addresses the hypothesis that IL-5 and eotaxin are critical in pulmonary eosinophil response related to FI-RSV vaccine-enhanced disease. The findings suggest that in addition to mediating tissue pathology, eosinophils within a Th2 environment also have antiviral activity.
authors.affiliation: Institute for Glycomics, Griffith University, Gold Coast, QLD, Australia Faculty of Education, Science, Technology and Mathematics, University of Canberra, Canberra, ACT, Australia.
authors.forename: Yung-Chang
authors.initials: YC
authors.lastname: Su
authors.affiliation: Faculty of Education, Science, Technology and Mathematics, University of Canberra, Canberra, ACT, Australia Department of Immunology, John Curtin School of Medical Research, Australian National University, Canberra, ACT, Australia.
authors.forename: Dijana
authors.initials: D
authors.lastname: Townsend
authors.affiliation: Institute for Glycomics, Griffith University, Gold Coast, QLD, Australia Faculty of Education, Science, Technology and Mathematics, University of Canberra, Canberra, ACT, Australia.
authors.forename: Lara J
authors.initials: LJ
authors.lastname: Herrero
authors.affiliation: Faculty of Education, Science, Technology and Mathematics, University of Canberra, Canberra, ACT, Australia.
authors.forename: Ali
authors.initials: A
authors.lastname: Zaid
authors.affiliation: Institute for Glycomics, Griffith University, Gold Coast, QLD, Australia Faculty of Education, Science, Technology and Mathematics, University of Canberra, Canberra, ACT, Australia.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Rolph
authors.affiliation: Faculty of Education, Science, Technology and Mathematics, University of Canberra, Canberra, ACT, Australia.
authors.forename: Michelle E
authors.initials: ME
authors.lastname: Gahan
authors.affiliation: Faculty of Education, Science, Technology and Mathematics, University of Canberra, Canberra, ACT, Australia.
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Nelson
authors.affiliation: Institute for Glycomics, Griffith University, Gold Coast, QLD, Australia.
authors.forename: Penny A
authors.initials: PA
authors.lastname: Rudd
authors.affiliation: Department of Translational Biosciences, John Curtin School of Medical Research, Australian National University, Canberra, ACT, Australia.
authors.forename: Klaus I
authors.initials: KI
authors.lastname: Matthaei
authors.affiliation: Priority Research Centre for Asthma and Respiratory Disease, Faculty of Health and Medicine and Hunter Medical Research Institute, University of Newcastle, Newcastle, NSW, Australia.
authors.forename: Paul S
authors.initials: PS
authors.lastname: Foster
authors.affiliation: School of Molecular and Biomedical Science, The University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Lindsay
authors.initials: L
authors.lastname: Dent
authors.affiliation: Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, Georgia, USA.
authors.forename: Ralph A
authors.initials: RA
authors.lastname: Tripp
authors.affiliation: Division of Pulmonary Medicine, Department of Biochemistry and Molecular Biology, Mayo Clinic Arizona, Scottsdale, Arizona, USA.
authors.forename: James
authors.initials: J
authors.lastname: Lee
authors.affiliation: Faculty of Education, Science, Technology and Mathematics, University of Canberra, Canberra, ACT, Australia.
authors.forename: Ljubov
authors.initials: L
authors.lastname: Simson
authors.affiliation: Institute for Glycomics, Griffith University, Gold Coast, QLD, Australia Faculty of Education, Science, Technology and Mathematics, University of Canberra, Canberra, ACT, Australia s.mahalingam@griffith.edu.au.
authors.forename: Suresh
authors.initials: S
authors.lastname: Mahalingam
mesh_terms: D000818:Animals; D004804:Eosinophils / Q000276:immunology*; D005260:Female; D008168:Lung / Q000276:immunology* / Q000473:pathology* / Q000821:virology; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology* / Q000473:pathology*; D022261:Respiratory Syncytial Virus Vaccines / Q000276:immunology*; D018113:Respiratory Syncytial Virus, Human / Q000276:immunology*; D015164:Vaccines, Inactivated / Q000276:immunology; D019562:Viral Load
chemical_list: D022261:Respiratory Syncytial Virus Vaccines; D015164:Vaccines, Inactivated