Enterovirus D68 infection induces IL-17–dependent neutrophilic airway inflammation and hyperresponsiveness
| Autor: | Amy P Callear, Emily T. Martin, Marc B. Hershenson, Qian Wu, J. Kelley Bentley, Tomoko Ishikawa, Terri Stillwell, Jing Lei, William T. Jackson, Charu Rajput, Mingyuan Han, Joanna L. Hinde |
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| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Neutrophils CCL2 medicine.disease_cause Mice 03 medical and health sciences 0302 clinical medicine RAR-related orphan receptor gamma Cell Line Tumor Nasopharynx Enterovirus Infections Animals Humans Medicine RNA Messenger Child Lung CCL11 Enterovirus Enterovirus D Human House dust mite biology business.industry Interleukin-17 Pyroglyphidae Infant Newborn Infant General Medicine Allergens respiratory system biology.organism_classification Asthma respiratory tract diseases CXCL1 Disease Models Animal 030104 developmental biology Child Preschool Immunology biology.protein Female Interleukin 17 Antibody Rhinovirus business Bronchoalveolar Lavage Fluid Research Article 030215 immunology |
| Zdroj: | JCI Insight. 3 |
| ISSN: | 2379-3708 |
| DOI: | 10.1172/jci.insight.121882 |
| Popis: | Enterovirus D68 (EV-D68) shares biologic features with rhinovirus (RV). In 2014, a nationwide outbreak of EV-D68 was associated with severe asthma-like symptoms. We sought to develop a mouse model of EV-D68 infection and determine the mechanisms underlying airway disease. BALB/c mice were inoculated intranasally with EV-D68 (2014 isolate), RV-A1B, or sham, alone or in combination with anti–IL-17A or house dust mite (HDM) treatment. Like RV-A1B, lung EV-D68 viral RNA peaked 12 hours after infection. EV-D68 induced airway inflammation, expression of cytokines (TNF-α, IL-6, IL-12b, IL-17A, CXCL1, CXCL2, CXCL10, and CCL2), and airway hyperresponsiveness, which were suppressed by anti–IL-17A antibody. Neutrophilic inflammation and airway responsiveness were significantly higher after EV-D68 compared with RV-A1B infection. Flow cytometry showed increased lineage–, NKp46–, RORγt+ IL-17+ILC3s and γδ T cells in the lungs of EV-D68–treated mice compared with those in RV-treated mice. EV-D68 infection of HDM-exposed mice induced additive or synergistic increases in BAL neutrophils and eosinophils and expression of IL-17, CCL11, IL-5, and Muc5AC. Finally, patients from the 2014 epidemic period with EV-D68 showed significantly higher nasopharyngeal IL-17 mRNA levels compared with patients with RV-A infection. EV-D68 infection induces IL-17–dependent airway inflammation and hyperresponsiveness, which is greater than that generated by RV-A1B, consistent with the clinical picture of severe asthma-like symptoms. |
| Databáze: | OpenAIRE |
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