IFN-α/IFN-λ responses to respiratory viruses in paediatric asthma.
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.
Dept of Molecular Pneumology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen, Erlangen, Germany.|These authors contributed equally to this paper.
Annika
A
Bergauer
Dept of Molecular Pneumology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen, Erlangen, Germany.|These authors contributed equally to this paper.
Nina
N
Sopel
Dept of Molecular Pneumology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen, Erlangen, Germany.
Bettina
B
Kroß
Dept of Virology, University of Turku, Turku, Finland.
Tytti
T
Vuorinen
Allergy and Clinical Immunology Unit, 2nd Paediatric Clinic, National and Kapodistrian University of Athens, Athens, Greece.
Paraskevi
P
Xepapadaki
Translational Genomics Core, Partners Biobank, Partners HealthCare, Personalized Medicine, Cambridge, MA, USA.
Scott T
ST
Weiss
Translational Genomics Core, Partners Biobank, Partners HealthCare, Personalized Medicine, Cambridge, MA, USA.
Ashley
A
Blau
Translational Genomics Core, Partners Biobank, Partners HealthCare, Personalized Medicine, Cambridge, MA, USA.
Himanshu
0000-0001-7133-6327
H
Sharma
Institute of Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen, Erlangen, Germany.
Cornelia
C
Kraus
Dept of Molecular Pneumology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen, Erlangen, Germany.
Rebekka
R
Springel
Children's Hospital, Dept of Paediatrics and Adolescent Medicine, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen, Erlangen, Germany.
Manfred
M
Rauh
Dept of Molecular Pneumology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen, Erlangen, Germany.
Susanne
S
Mittler
Dept of Molecular Pneumology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen, Erlangen, Germany.
Anna
A
Graser
Children's Hospital, Dept of Allergy and Pneumology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen, Erlangen, Germany.
Theodor
T
Zimmermann
Children's Hospital, Dept of Allergy and Pneumology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen, Erlangen, Germany.
Volker O
VO
Melichar
Children's Hospital, Dept of Allergy and Pneumology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen, Erlangen, Germany.
Alexander
A
Kiefer
Dept of Immunology, Rheumatology and Allergy, Medical University of Łódź, Łódź, Poland.
Marek L
ML
Kowalski
Dept of Immunology, Rheumatology and Allergy, Medical University of Łódź, Łódź, Poland.
Anna
A
Sobanska
Dept of Paediatrics and Adolescent Medicine, Turku University Hospital, Turku, Finland.
Tuomas
T
Jartti
Dept of Paediatrics and Adolescent Medicine, Turku University Hospital, Turku, Finland.|Research Centre of Applied and Preventive Cardiovascular Medicine, Turku University Hospital, Turku, Finland.
Heikki
H
Lukkarinen
Allergy and Clinical Immunology Unit, 2nd Paediatric Clinic, National and Kapodistrian University of Athens, Athens, Greece.|Division of Infection, Immunity and Respiratory Medicine, The University of Manchester, Manchester, UK.
Nikolaos G
NG
Papadopoulos
Dept of Molecular Pneumology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen, Erlangen, Germany Susetta.Finotto@uk-erlangen.de.
Susetta
S
Finotto
D001249:Asthma / Q000276:immunology* / Q000821:virology; D002097:C-Reactive Protein / Q000032:analysis*; D002478:Cells, Cultured; D002675:Child, Preschool; D018450:Disease Progression; D005060:Europe; D005260:Female; D006801:Humans; D050856:Interferon Regulatory Factor-1 / Q000235:genetics; D007372:Interferons / Q000097:blood* / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000821:virology*; D008297:Male; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics; D009305:Nasopharynx / Q000821:virology; D010850:Picornaviridae Infections / Q000276:immunology*; D011446:Prospective Studies; D012333:RNA, Messenger / Q000032:analysis; D012229:Rhinovirus; D050794:STAT1 Transcription Factor / Q000235:genetics; D050795:STAT2 Transcription Factor / Q000235:genetics; D015398:Signal Transduction
C494257:IRF1 protein, human; D050856:Interferon Regulatory Factor-1; C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; D012333:RNA, Messenger; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050795:STAT2 Transcription Factor; C494084:STAT2 protein, human; D002097:C-Reactive Protein; D007372:Interferons