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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Respiratory Syncytial Virus Vaccines
antiviral properties
Respiratory Syncytial Viruses
eosinophils
Eosinophils
Antiviral Agents
Interleukin-5
interleukin-5
Pulmonary Eosinophilia
lungs
Formaldehyde
vaccines
formalin
Lung
viruses
eosinophilia
inflammation
mice
Pneumonia
Vaccination

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Su, S. Y-C., Townsend, D., Herrero, L., Zaid, A., Rolph, M., GAHAN, M., ... 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
Su, Steve Yung-Chang ; Townsend, Dijana ; Herrero, Lara ; Zaid, Ali ; Rolph, Michael ; GAHAN, Michelle ; Nelson, Michelle ; Rudd, Penny ; Matthaei, Klaus ; Foster, Paul ; Dent, Lindsay ; Tripp, Ralph ; Lee, James ; SIMSON, Luby ; Mahalingam, Suresh. / Dual proinflammatory and antiviral properties of pulmonary eosinophils in respiratory syncytial virus vaccine-enhanced disease. In: Journal of Virology. 2015 ; Vol. 89, No. 3. pp. 1564-1578.
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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. 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.",
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Su, SY-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, vol. 89, no. 3, pp. 1564-1578. https://doi.org/10.1128/JVI.01536-14

Dual proinflammatory and antiviral properties of pulmonary eosinophils in respiratory syncytial virus vaccine-enhanced disease. / Su, Steve Yung-Chang; Townsend, Dijana; Herrero, Lara; Zaid, Ali; Rolph, Michael; GAHAN, Michelle; Nelson, Michelle; Rudd, Penny; Matthaei, Klaus; Foster, Paul; Dent, Lindsay; Tripp, Ralph; Lee, James; SIMSON, Luby; Mahalingam, Suresh.

In: Journal of Virology, Vol. 89, No. 3, 2015, p. 1564-1578.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Dual proinflammatory and antiviral properties of pulmonary eosinophils in respiratory syncytial virus vaccine-enhanced disease

AU - Su, Steve Yung-Chang

AU - Townsend, Dijana

AU - Herrero, Lara

AU - Zaid, Ali

AU - Rolph, Michael

AU - GAHAN, Michelle

AU - Nelson, Michelle

AU - Rudd, Penny

AU - Matthaei, Klaus

AU - Foster, Paul

AU - Dent, Lindsay

AU - Tripp, Ralph

AU - Lee, James

AU - SIMSON, Luby

AU - Mahalingam, Suresh

N1 - Copyright © 2015, American Society for Microbiology. All Rights Reserved.

PY - 2015

Y1 - 2015

N2 - 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.

AB - 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.

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U2 - 10.1128/JVI.01536-14

DO - 10.1128/JVI.01536-14

M3 - Article

VL - 89

SP - 1564

EP - 1578

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 3

ER -