Raised interferon-β, type 3 interferon and interferon-stimulated genes - evidence of innate immune activation in neutrophilic asthma

Clin Exp Allergy. 2017 Mar;47(3):313-323. doi: 10.1111/cea.12809. Epub 2016 Oct 14.

Abstract

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.

Conclusion and clinical relevance: 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.

Keywords: asthma phenotype; eosinophils; interferon-stimulated genes; interferon-β and interferon-λ; neutrophils.

MeSH terms

  • Adrenal Cortex Hormones / therapeutic use
  • Adult
  • Aged
  • Anti-Asthmatic Agents / therapeutic use
  • Asthma / diagnosis
  • Asthma / drug therapy
  • Asthma / etiology*
  • Asthma / metabolism*
  • Case-Control Studies
  • Female
  • Gene Expression Regulation*
  • Humans
  • Immunity, Innate
  • Immunoglobulin E / blood
  • Immunoglobulin E / immunology
  • Interferon Regulatory Factors / genetics*
  • Interferon-beta / metabolism*
  • Interferons / metabolism*
  • Male
  • Middle Aged
  • Neutrophil Activation / immunology
  • Neutrophils / immunology
  • Neutrophils / metabolism
  • Phenotype
  • Respiratory Function Tests
  • Risk Factors
  • Severity of Illness Index
  • Sputum / immunology
  • Sputum / metabolism
  • Sputum / virology

Substances

  • Adrenal Cortex Hormones
  • Anti-Asthmatic Agents
  • Interferon Regulatory Factors
  • Immunoglobulin E
  • Interferon-beta
  • Interferons

Associated data

  • GENBANK/NM_172140.1