Raised interferon-β, type 3 interferon and interferon-stimulated genes - evidence of innate immune activation in neutrophilic asthma.
BACKGROUND
Interferons play an important role in innate immunity. Previous studies report deficiency in virus induction of interferon (IFN)-α, IFN-β and IFN-λ in bronchial epithelial and bronchial lavage cells in atopic asthmatics. It is now recognized that asthma is a heterogeneous disease comprising different inflammatory phenotypes, some of which may involve innate immune activation in the absence of overt infection.


OBJECTIVE
The aim of this study was to investigate whether the severity of asthma or a specific cellular sputum pattern may be linked to evidence of innate immune activation.


METHODS
Here we investigate the expression of IFN-β, IFN-λ1 (IL-29), IFN-λ2/3 (IL-28A/B) and the interferon-stimulated genes (ISGs) such as myxovirus resistance 1 (Mx1), oligoadenylate synthetase (OAS) and viperin in unstimulated sputum cells in 57 asthmatics (including 16 mild, 19 moderate and 22 severe asthma patients) and compared them with 19 healthy subjects.


RESULTS
We observed increased expression of IFN-β, IFN-λ1/IL-29, OAS and viperin in asthmatics compared with healthy subjects, while IL-28 was not expressed in any group. The overexpression was restricted to neutrophilic asthmatics (sputum neutrophils ≥ 76%), while eosinophilic asthmatics (sputum eosinophils ≥ 3%) did not differ from healthy subjects or even showed a lower expression of Mx1. No difference in interferon or ISG expression was observed according to clinical asthma severity.


CONCLUSIONS
Neutrophilic, but not eosinophilic, asthmatics display overexpression of IFN-β, IFN-λ1/IL-29 and ISGs in their sputum cells that may reflect ongoing innate immune activation.
Department of Respiratory Medicine, CHU Liege, GIGA I3 University of Liege, Liege, Belgium.|Allergy Service, University Hospital Professor Polydoro Ernani de São Thiago, Federal University of Santa Catarina (HU-UFSC), Florianopolis, SC, Brazil.
J
J
da Silva
Department of Respiratory Medicine, CHU Liege, GIGA I3 University of Liege, Liege, Belgium.|Airway Disease Infection Section, National Heart and Lung Institute, Imperial College London, London, UK.
C
C
Hilzendeger
Department of Respiratory Medicine, CHU Liege, GIGA I3 University of Liege, Liege, Belgium.
C
C
Moermans
Department of Respiratory Medicine, CHU Liege, GIGA I3 University of Liege, Liege, Belgium.
F
F
Schleich
Department of Respiratory Medicine, CHU Liege, GIGA I3 University of Liege, Liege, Belgium.
M
M
Henket
Airway Disease Infection Section, National Heart and Lung Institute, Imperial College London, London, UK.
T
T
Kebadze
Airway Disease Infection Section, National Heart and Lung Institute, Imperial College London, London, UK.
P
P
Mallia
Airway Disease Infection Section, National Heart and Lung Institute, Imperial College London, London, UK.
M R
MR
Edwards
Airway Disease Infection Section, National Heart and Lung Institute, Imperial College London, London, UK.
S L
SL
Johnston
Department of Respiratory Medicine, CHU Liege, GIGA I3 University of Liege, Liege, Belgium.
R
R
Louis
D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use; D001249:Asthma / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism*; D016022:Case-Control Studies; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007113:Immunity, Innate; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D050835:Interferon Regulatory Factors / Q000235:genetics*; D016899:Interferon-beta / Q000378:metabolism*; D007372:Interferons / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D018375:Neutrophil Activation / Q000276:immunology; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D010641:Phenotype; D012129:Respiratory Function Tests; D012307:Risk Factors; D012720:Severity of Illness Index; D013183:Sputum / Q000276:immunology / Q000378:metabolism / Q000821:virology
D000305:Adrenal Cortex Hormones; D018927:Anti-Asthmatic Agents; D050835:Interferon Regulatory Factors; D007073:Immunoglobulin E; D016899:Interferon-beta; D007372:Interferons
asthma phenotype; eosinophils; interferon-stimulated genes; interferon-β and interferon-λ; neutrophils