Dual proinflammatory and antiviral properties of pulmonary eosinophils in respiratory syncytial virus vaccine-enhanced disease

Steve Yung-Chang Su, Dijana Townsend, Lara Herrero, Ali Zaid, Michael Rolph, Michelle GAHAN, Michelle Nelson, Penny Rudd, Klaus Matthaei, Paul Foster, Lindsay Dent, Ralph Tripp, James Lee, Luby SIMSON, Suresh Mahalingam

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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. IMPORTANCE 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.
Original languageEnglish
Pages (from-to)1564-1578
Number of pages15
JournalJournal of Virology
Volume89
Issue number3
DOIs
Publication statusPublished - 2015

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    Su, S. Y-C., Townsend, D., Herrero, L., Zaid, A., Rolph, M., GAHAN, M., Nelson, M., Rudd, P., Matthaei, K., Foster, P., Dent, L., Tripp, R., Lee, J., SIMSON, L., & Mahalingam, S. (2015). Dual proinflammatory and antiviral properties of pulmonary eosinophils in respiratory syncytial virus vaccine-enhanced disease. Journal of Virology, 89(3), 1564-1578. https://doi.org/10.1128/JVI.01536-14