title: CCL7 and IRF-7 Mediate Hallmark Inflammatory and IFN Responses following Rhinovirus 1B Infection.
abstract: Rhinovirus (RV) infections are common and have the potential to exacerbate asthma. We have determined the lung transcriptome in RV strain 1B-infected naive BALB/c mice (nonallergic) and identified CCL7 and IFN regulatory factor (IRF)-7 among the most upregulated mRNA transcripts in the lung. To investigate their roles we employed anti-CCL7 Abs and an IRF-7-targeting small interfering RNA in vivo. Neutralizing CCL7 or inhibiting IRF-7 limited neutrophil and macrophage influx and IFN responses in nonallergic mice. Neutralizing CCL7 also reduced activation of NF-κB p65 and p50 subunits, as well as airway hyperreactivity (AHR) in nonallergic mice. However, neither NF-κB subunit activation nor AHR was abolished with infection of allergic mice after neutralizing CCL7, despite a reduction in the number of neutrophils, macrophages, and eosinophils. IRF-7 small interfering RNA primarily suppressed IFN-α and IFN-β levels during infection of allergic mice. Our data highlight a pivotal role of CCL7 and IRF-7 in RV-induced inflammation and IFN responses and link NF-κB signaling to the development of AHR.
authors.affiliation: Experimental and Translational Respiratory Medicine Group, University of Newcastle and Hunter Medical Research Institute, Newcastle, New South Wales 2305, Australia; Priority Research Centre for Asthma and Respiratory Diseases, University of Newcastle, Newcastle, New South Wales 2305, Australia;
authors.forename: Jason
authors.initials: J
authors.lastname: Girkin
authors.affiliation: Experimental and Translational Respiratory Medicine Group, University of Newcastle and Hunter Medical Research Institute, Newcastle, New South Wales 2305, Australia; Priority Research Centre for Asthma and Respiratory Diseases, University of Newcastle, Newcastle, New South Wales 2305, Australia;
authors.forename: Luke
authors.initials: L
authors.lastname: Hatchwell
authors.affiliation: Priority Research Centre for Asthma and Respiratory Diseases, University of Newcastle, Newcastle, New South Wales 2305, Australia;
authors.forename: Paul
authors.initials: P
authors.lastname: Foster
authors.affiliation: Airway Disease Infection Section, National Heart and Lung Institute, Medical Research Council and Asthma UK Centre in Allergic Mechanisms of Asthma, Imperial College London, London W2 1PG, United Kingdom; and.
authors.forename: Sebastian L
authors.initials: SL
authors.lastname: Johnston
authors.affiliation: Airway Disease Infection Section, National Heart and Lung Institute, Medical Research Council and Asthma UK Centre in Allergic Mechanisms of Asthma, Imperial College London, London W2 1PG, United Kingdom; and.
authors.forename: Nathan
authors.initials: N
authors.lastname: Bartlett
authors.affiliation: Experimental and Translational Respiratory Medicine Group, University of Newcastle and Hunter Medical Research Institute, Newcastle, New South Wales 2305, Australia; Priority Research Centre for Asthma and Respiratory Diseases, University of Newcastle, Newcastle, New South Wales 2305, Australia;
authors.forename: Adam
authors.initials: A
authors.lastname: Collison
authors.affiliation: Experimental and Translational Respiratory Medicine Group, University of Newcastle and Hunter Medical Research Institute, Newcastle, New South Wales 2305, Australia; Priority Research Centre for Asthma and Respiratory Diseases, University of Newcastle, Newcastle, New South Wales 2305, Australia; Paediatric Respiratory and Sleep Medicine Unit, Newcastle Children's Hospital, Kaleidoscope, Newcastle, New South Wales 2305, Australia Joerg.Mattes@newcastle.edu.au.
authors.forename: Joerg
authors.initials: J
authors.lastname: Mattes
mesh_terms: D000818:Animals; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000821:virology; D054410:Chemokine CCL7 / Q000276:immunology*; D003139:Common Cold / Q000276:immunology*; D004195:Disease Models, Animal; D005434:Flow Cytometry; D007249:Inflammation / Q000276:immunology / Q000821:virology; D050839:Interferon Regulatory Factor-7 / Q000276:immunology*; D007372:Interferons / Q000276:immunology*; D008168:Lung / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000276:immunology; D060888:Real-Time Polymerase Chain Reaction; D012229:Rhinovirus / Q000276:immunology; D059467:Transcriptome
chemical_list: C515451:Ccl7 protein, mouse; D054410:Chemokine CCL7; D050839:Interferon Regulatory Factor-7; C494235:Irf7 protein, mouse; D016328:NF-kappa B; D007372:Interferons
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