Identification of IFN-γ and IL-27 as Critical Regulators of Respiratory Syncytial Virus-Induced Exacerbation of Allergic Airways Disease in a Mouse Model.
J Immunol
; 200(1): 237-247, 2018 01 01.
Article
em En
| MEDLINE
| ID: mdl-29167232
ABSTRACT
Respiratory syncytial virus (RSV) infection induces asthma exacerbations, which leads to worsening of clinical symptoms and may result in a sustained decline in lung function. Exacerbations are the main cause of morbidity and mortality associated with asthma, and significantly contribute to asthma-associated healthcare costs. Although glucocorticoids are used to manage exacerbations, some patients respond to them poorly. The underlying mechanisms associated with steroid-resistant exacerbations remain largely unknown. We have previously established a mouse model of RSV-induced exacerbation of allergic airways disease, which mimics hallmark clinical features of asthma. In this study, we have identified key roles for macrophage IFN-γ and IL-27 in the regulation of RSV-induced exacerbation of allergic airways disease. Production of IFN-γ and IL-27 was steroid-resistant, and neutralization of IFN-γ or IL-27 significantly suppressed RSV-induced steroid-resistant airway hyperresponsiveness and airway inflammation. We have previously implicated activation of pulmonary macrophage by TNF-α and/or MCP-1 in the mechanisms of RSV-induced exacerbation. Stimulation of pulmonary macrophages with TNF-α and/or MCP-1 induced expression of both IFN-γ and IL-27. Our findings highlight critical roles for IFN-γ and IL-27, downstream of TNF-α and MCP-1, in the mechanism of RSV-induced exacerbation. Thus, targeting the pathways that these factors activate may be a potential therapeutic approach for virus-induced asthma exacerbations.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Vírus Sinciciais Respiratórios
/
Asma
/
Interferon gama
/
Macrófagos Alveolares
/
Infecções por Vírus Respiratório Sincicial
/
Interleucina-27
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
J Immunol
Ano de publicação:
2018
Tipo de documento:
Article