Respiratory virus induction of alpha‐, beta‐ and lambda‐interferons in bronchial epithelial cells and peripheral blood mononuclear cells

Abstract

Respiratory virus infections are major triggers of acute exacerbations of asthma in both adults and children, implicated in around 80% of paediatric (1) and 75% of adult (2) asthma attacks. They are therefore major causes of asthma morbidity and mortality (3). Of viruses detected in asthma exacerbations, two thirds are rhinoviruses (1). Influenza viruses are also implicated in asthma exacerbations during annual influenza epidemics (2,4,5).Current therapy of asthma exacerbations is of limited efficacy (6-8), new approaches are therefore required.Background: Respiratory viruses, predominantly rhinoviruses are the major cause of asthma exacerbations. Impaired production of interferon-b in rhinovirus infected bronchial epithelial cells (BECs) and of the newly discovered interferon-ks in both BECs and bronchoalveolar lavage cells, is implicated in asthma exacerbation pathogenesis. Thus replacement of deficient interferon is a candidate new therapy for asthma exacerbations. Rhinoviruses and other respiratory viruses infect both BECs and macrophages, but their relative capacities for a-, b-and k-interferon production are unknown. Methods: To provide guidance regarding which interferon type is the best candidate for development for treatment/prevention of asthma exacerbations we investigated respiratory virus induction of a-, b-and k-interferons in BECs and peripheral blood mononuclear cells (PBMCs) by reverse transferase-polymerase chain reaction and enzyme-linked immunosorbent assay. Results: Rhinovirus infection of BEAS-2B BECs induced interferon-a mRNA expression transiently at 8 h and interferon-b later at 24 h while induction of interferon-k was strongly induced at both time points. At 24 h, interferon-a protein was not detected, interferon-b was weakly induced while interferon-k was strongly induced. Similar patterns of mRNA induction were observed in primary BECs, in response to both rhinovirus and influenza A virus infection, though protein levels were below assay detection limits. In PBMCs interferon-a, interferon-b and interferon-k mRNAs were all strongly induced by rhinovirus at both 8 and 24 h and proteins were induced: interferon-a>-b>-k. Thus respiratory viruses induced expression of a-, b-and k-interferons in BECs and PBMCs. In PBMCs interferon-a>-b>-k while in BECs, interferon-k>-b>-a. Conclusions: We conclude that interferon-ks are likely the principal interferons produced during innate responses to respiratory viruses in BECs and interferonas in PBMCs, while interferon-b is produced by both cell types.

The impact of pandemic influenza A (H1N1) 2009 on the circulation of respiratory viruses 2009–2011

“…However, the magnitude of the activity in different age groups required for the interaction to become epidemiologically visible remained to be determined. The interactivity between influenza virus and other respiratory viruses might be mediated by the antiviral state of the receptor cells 6 . It was shown that once influenza virus infection becomes established, infected cells start producing interferon and other cytokines to cause the cells to enter an antiviral state.…”

Novel antiviral properties of azithromycin in cystic fibrosis airway epithelial cells

“…The airway epithelium is central in the antiviral defence of the lung by producing IFNs upon infection with RVs, leading to the induction of ISGs that directly interfere with virus replication [13,14]. In vitro and in vivo, type I IFN is important in the host defence against RV, with pre-treatment of endogenous IFN robustly reducing virus load in in vitro cell culture models [15][16][17].…”

Regulation of IFN-λ1 Promoter Activity (IFN-λ1/IL-29) in Human Airway Epithelial Cells

“…Expression of IFN-l is restricted mainly to plasmacytoid dendritic cells and epithelial cells (8,9). Furthermore, expression of the IFN-l receptor (in which both chains are distinct from those used in either the type I or type II IFNRs) is almost completely restricted to immune cells and epithelial cells (9)(10)(11)(12).…”