title: Human and Mouse Eosinophils Have Antiviral Activity against Parainfluenza Virus.
abstract: Respiratory viruses cause asthma exacerbations. Because eosinophils are the prominent leukocytes in the airways of 60-70% of patients with asthma, we evaluated the effects of eosinophils on a common respiratory virus, parainfluenza 1, in the lung. Eosinophils recruited to the airways of wild-type mice after ovalbumin sensitization and challenge significantly decreased parainfluenza virus RNA in the lungs 4 days after infection compared with nonsensitized animals. This antiviral effect was also seen in IL-5 transgenic mice with an abundance of airway eosinophils (NJ.1726) but was lost in transgenic eosinophil-deficient mice (PHIL) and in IL-5 transgenic mice crossed with eosinophil-deficient mice (NJ.1726-PHIL). Loss of the eosinophil granule protein eosinophil peroxidase, using eosinophil peroxidase-deficient transgenic mice, did not reduce eosinophils' antiviral effect. Eosinophil antiviral mechanisms were also explored in vitro. Isolated human eosinophils significantly reduced parainfluenza virus titers. This effect did not involve degradation of viral RNA by eosinophil granule RNases. However, eosinophils treated with a nitric oxide synthase inhibitor lost their antiviral activity, suggesting eosinophils attenuate viral infectivity through production of nitric oxide. Consequently, eosinophil nitric oxide production was measured with an intracellular fluorescent probe. Eosinophils produced nitric oxide in response to virus and to a synthetic agonist of the virus-sensing innate immune receptor, Toll-like receptor (TLR) 7. IFNγ increased expression of eosinophil TLR7 and potentiated TLR7-induced nitric oxide production. These results suggest that eosinophils promote viral clearance in the lung and contribute to innate immune responses against respiratory virus infections in humans.
authors.affiliation: 1 Division of Pulmonary and Critical Care Medicine, Oregon Health & Science University, Portland, Oregon.
authors.forename: Matthew G
authors.initials: MG
authors.lastname: Drake
authors.affiliation: 1 Division of Pulmonary and Critical Care Medicine, Oregon Health & Science University, Portland, Oregon.
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Bivins-Smith
authors.affiliation: 1 Division of Pulmonary and Critical Care Medicine, Oregon Health & Science University, Portland, Oregon.
authors.forename: Becky J
authors.identifier: 0000-0002-7803-6447
authors.initials: BJ
authors.lastname: Proskocil
authors.affiliation: 1 Division of Pulmonary and Critical Care Medicine, Oregon Health & Science University, Portland, Oregon.
authors.forename: Zhenying
authors.initials: Z
authors.lastname: Nie
authors.affiliation: 2 Department of Pathology, Stanford University School of Medicine, Stanford, California.
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Scott
authors.affiliation: 3 Department of Biochemistry and Molecular Biology, Division of Pulmonary Medicine, and.
authors.forename: James J
authors.initials: JJ
authors.lastname: Lee
authors.affiliation: 4 Department of Biochemistry and Molecular Biology, Divisions of Hematology and Oncology, Mayo Clinic in Arizona, Scottsdale, Arizona.
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Lee
authors.affiliation: 1 Division of Pulmonary and Critical Care Medicine, Oregon Health & Science University, Portland, Oregon.
authors.forename: Allison D
authors.initials: AD
authors.lastname: Fryer
authors.affiliation: 1 Division of Pulmonary and Critical Care Medicine, Oregon Health & Science University, Portland, Oregon.
authors.forename: David B
authors.initials: DB
authors.lastname: Jacoby
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000276:immunology*; D004804:Eosinophils / Q000201:enzymology / Q000276:immunology*; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000473:pathology / Q000821:virology; D008253:Macaca mulatta; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000378:metabolism; D010047:Ovalbumin / Q000276:immunology; D018184:Paramyxoviridae Infections / Q000276:immunology / Q000821:virology; D018098:Paramyxovirinae / Q000276:immunology* / Q000472:pathogenicity; D009195:Peroxidase / Q000378:metabolism; D012260:Ribonucleases / Q000378:metabolism; D051199:Toll-Like Receptor 7 / Q000378:metabolism
chemical_list: D000998:Antiviral Agents; D051199:Toll-Like Receptor 7; D009569:Nitric Oxide; D007371:Interferon-gamma; D010047:Ovalbumin; D009195:Peroxidase; D012260:Ribonucleases
keywords: Toll-like receptor 7; asthma; eosinophil; nitric oxide; parainfluenza virus