Transforming growth factor-beta enhances rhinovirus infection by diminishing early innate responses
| Autor: | Reena Ghildyal, Hayat Dagher, Philip G. Bardin, Belinda J. Thomas, Mandy Lee Lindsay, Dongsheng Li, Nicholas Freezer |
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| Rok vydání: | 2009 |
| Předmět: |
Pulmonary and Respiratory Medicine
Adult Chemokine Rhinovirus Neutrophils viruses Clinical Biochemistry Respiratory Mucosa medicine.disease_cause Virus Replication Microbiology Proinflammatory cytokine Transforming Growth Factor beta1 Immune system stomatognathic system Interferon medicine Humans Child Molecular Biology Cells Cultured Picornaviridae Infections biology Cell Death Interleukin-8 Cell Differentiation Cell Biology Transforming growth factor beta respiratory system Fibroblasts Asthma Immunity Innate respiratory tract diseases Viral replication Immunology Interferon Type I biology.protein Interferon Regulatory Factor-3 Chemokines Transforming growth factor medicine.drug Signal Transduction |
| Zdroj: | American journal of respiratory cell and molecular biology. 41(3) |
| ISSN: | 1535-4989 |
| Popis: | Individuals with asthma are prone to viral and bacterial infections, and most asthma exacerbations have been linked to viruses, particularly rhinovirus. Excess transforming growth factor (TGF)-beta present in asthmatic airways may cause immune suppression, as well as transdifferentiate fibroblasts to myofibroblasts, thereby augmenting proinflammatory responses after rhinovirus infection. After rhinovirus infection we examined virus replication and host cell immune responses in airway fibroblasts in the presence of TGF-beta1 and in myofibroblasts. Primary culture fibroblasts were pretreated with TGF-beta1 or transdifferentiated into myofibroblasts, and then infected with rhinovirus. Viral replication, virus release, chemokine production, and interferon (IFN) responses were measured over 72 hours. Rhinovirus replication and virus release into supernatants were enhanced in fibroblasts incubated with TGF-beta1 and in fibroblasts obtained from patients with asthma. Myofibroblasts also showed more rhinovirus replication, and infected myofibroblasts produced excess neutrophil chemokines. Examination of innate responses revealed blunting of type I IFN reactions with dissociated viral RNA and IFN mRNA responses. Addition of type I IFN restituted antiviral responses, and the effect of TGF-beta1 appeared to be mediated via actions on IFN regulatory factor-3 pathways. These data demonstrate that TGF-beta1 mediates enhanced virus replication and proinflammatory responses in airway cells. TGF-beta may act as an endogenous immunosuppressant promoting virus replication and inflammation during the evolution of acute severe asthma associated with rhinovirus infection. |
| Databáze: | OpenAIRE |
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