RESUMO
We analysed the influence of rhinovirus (RV) in nasopharyngeal fluid (NPF) on type I and III interferon (IFN) responses (e.g. IFN-α and IFN -: λ) and their signal transduction, at baseline and during disease exacerbation, in cohorts of pre-school children with and without asthma.At the time of recruitment into the Europe-wide study PreDicta, and during symptoms, NPF was collected and the local RV colonisation was analysed. Peripheral blood mononuclear cells (PBMCs) were challenged in vitro with RV or not. RNA was analysed by quantitative real-time PCR and gene arrays. Serum was analysed with ELISA for IFNs and C-reactive protein.We found that PBMCs from asthmatic children infected in vitro with the RV1b serotype upregulated MYD88, IRF1, STAT1 and STAT2 mRNA, whereas MYD88, IRF1, STAT1 and IRF9 were predominantly induced in control children. Moreover, during symptomatic visits because of disease exacerbation associated with RV detection in NPF, IFN-α production was found increased, while IFN-λ secretion was already induced by RV in asthmatic children at baseline.During asthma exacerbations associated with RV, asthmatic children can induce IFN-α secretion, indicating a hyperactive immune response to repeated respiratory virus infection.
Assuntos
Asma/imunologia , Proteína C-Reativa/análise , Interferons/sangue , Leucócitos Mononucleares/virologia , Infecções por Picornaviridae/imunologia , Asma/virologia , Células Cultivadas , Pré-Escolar , Progressão da Doença , Europa (Continente) , Feminino , Humanos , Fator Regulador 1 de Interferon/genética , Interferons/imunologia , Masculino , Fator 88 de Diferenciação Mieloide/genética , Nasofaringe/virologia , Estudos Prospectivos , RNA Mensageiro/análise , Rhinovirus , Fator de Transcrição STAT1/genética , Fator de Transcrição STAT2/genética , Transdução de SinaisAssuntos
Asma/etiologia , Asma/metabolismo , Interações Hospedeiro-Patógeno/imunologia , Infecções por Picornaviridae/complicações , Infecções por Picornaviridae/imunologia , Rhinovirus/imunologia , Fator de Crescimento Transformador beta/metabolismo , Animais , Asma/diagnóstico , Asma/terapia , Modelos Animais de Doenças , Humanos , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Camundongos , Infecções por Picornaviridae/virologia , Carga ViralAssuntos
Interferons , Rhinovirus , Antivirais , Asma , Genótipo , Humanos , Infecções por PicornaviridaeRESUMO
This corrects the article DOI: 10.1038/srep43426.
RESUMO
Here we investigated the relationship between local bacterial colonization and anti-bacterial immune responses in pre-school asthmatic and control children within the EU-wide study PreDicta. In this cohort of pre-school asthmatic children, nasopharyngeal colonization with Gram-negative bacteria such as Haemophilus influenzae and Moraxella catarrhalis was found to be associated with the highest interferon beta (IFNß) and IL-33 levels in the nasal pharyngeal fluids (NPF). IL33R-ST2 was found induced in the blood of asthmatic children with additional Gram + bacteria in the nasopharynx (Gr+/-). Furthermore, asthmatic children had more episodes of infection that required antibiotic therapy than the control group. Treatment with antibiotics associated with reduced ST2 in blood cells of both asthmatic and control children and reduced IL-33 levels in the airways of asthmatic children. In the absence of Staphylococcus (S.) aureus in NPF, antibiotic therapy associated with decreased IL-33 levels in the NPF and lower ST2 values in the blood of control children but not of asthmatic children. These data suggest that, in asthmatic children, Gram- bacteria, which persist after antibiotic therapy, contributes to IL-33 locally and associated with Gr + bacteria colonization in the airways, inhibited IFN-ß and in the absence of Staphylococcus (S.) aureus, induced ST2 bearing cells in their blood.