| Title | CCL7 and IRF-7 Mediate Hallmark Inflammatory and IFN Responses following Rhinovirus 1B Infection. | ||
| Author | Girkin, Jason; Hatchwell, Luke; Foster, Paul; Johnston, Sebastian L; Bartlett, Nathan; Collison, Adam; Mattes, Joerg | ||
| Journal | J Immunol | Publication Year/Month | 2015-May |
| PMID | 25847975 | PMCID | PMC4417644 |
| Affiliation + expend | 1.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;;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;;Priority Research Centre for Asthma and Respiratory Diseases, University of Newcastle, Newcastle, New South Wales 2305, Australia;;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. | ||
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-kappaB p65 and p50 subunits, as well as airway hyperreactivity (AHR) in nonallergic mice. However, neither NF-kappaB 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-alpha and IFN-beta 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-kappaB signaling to the development of AHR.