title: Sustained inflammation and differential expression of interferons type I and III in PVM-infected interferon-gamma (IFNγ) gene-deleted mice.
abstract: Interferon gamma (IFNγ) has complex immunomodulatory and antiviral properties. While IFNγ is detected in the airways in response to infection with the pneumovirus pathogen, pneumonia virus of mice (PVM; Family Paramyxoviridae), its role in promoting disease has not been fully explored. Here, we evaluate PVM infection in IFNγ(-/-) mice. Although the IFNγ gene-deletion has no impact on weight loss, survival or virus kinetics, expression of IFNβ, IFNλ2/3 and IFN-stimulated 2-5' oligoadenylate synthetases was significantly diminished compared to wild-type counterparts. Furthermore, PVM infection in IFNγ(-/-) mice promoted prominent inflammation, including eosinophil and neutrophil infiltration into the airways and lung parenchyma, observed several days after peak virus titer. Potential mechanisms include over-production of chemoattractant and eosinophil-active cytokines (CXCL1, CCL11, CCL3 and IL5) in PVM-infected IFNγ(-/-) mice; likewise, IFNγ actively antagonized IL5-dependent eosinophil survival ex vivo. Our results may have clinical implications for pneumovirus infection in individuals with IFNγ signaling defects.
authors.affiliation: Inflammation Immunobiology Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Stephanie F
authors.initials: SF
authors.lastname: Glineur
authors.affiliation: Inflammation Immunobiology Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Aaron B
authors.initials: AB
authors.lastname: Bowen
authors.affiliation: Inflammation Immunobiology Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Caroline M
authors.initials: CM
authors.lastname: Percopo
authors.affiliation: Inflammation Immunobiology Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Katia E
authors.initials: KE
authors.lastname: Garcia-Crespo
authors.affiliation: Inflammation Immunobiology Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Kimberly D
authors.initials: KD
authors.lastname: Dyer
authors.affiliation: Division of Pulmonary Medicine, Department of Biochemistry and Molecular Biology, Mayo Clinic Arizona, Scottsdale, AZ, 85259, USA.
authors.forename: Sergei I
authors.initials: SI
authors.lastname: Ochkur
authors.affiliation: Division of Pulmonary Medicine, Department of Biochemistry and Molecular Biology, Mayo Clinic Arizona, Scottsdale, AZ, 85259, USA.
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Lee
authors.affiliation: Division of Pulmonary Medicine, Department of Biochemistry and Molecular Biology, Mayo Clinic Arizona, Scottsdale, AZ, 85259, USA.
authors.forename: James J
authors.initials: JJ
authors.lastname: Lee
authors.affiliation: Department of Pediatrics, State University of New York Upstate Medical University, Syracuse, NY 13210, USA.
authors.forename: Joseph B
authors.initials: JB
authors.lastname: Domachowske
authors.affiliation: Inflammation Immunobiology Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Helene F
authors.initials: HF
authors.lastname: Rosenberg
mesh_terms: D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004804:Eosinophils / Q000166:cytology; D017353:Gene Deletion; D015967:Gene Expression Regulation, Viral / Q000276:immunology*; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D007370:Interferon Type I / Q000235:genetics / Q000378:metabolism*; D016899:Interferon-beta / Q000235:genetics / Q000378:metabolism; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D029122:Murine pneumonia virus / Q000235:genetics / Q000276:immunology*; D018186:Pneumovirus Infections / Q000378:metabolism / Q000473:pathology*; D007378:Interleukins; D000095022:Interferon Lambda
chemical_list: D016207:Cytokines; D007370:Interferon Type I; D016899:Interferon-beta; D007371:Interferon-gamma; C511668:interferon-lambda protein, mouse; D007378:Interleukins; D000095022:Interferon Lambda
keywords: Eosinophils; Inflammation; Interferon; Pneumovirus