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

Respiratory viruses, predominantly rhinoviruses are the major cause of asthma exacerbations. Impaired production of interferon-β in rhinovirus infected bronchial epithelial cells (BECs) and of the newly discovered interferon-λs 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 α-, β- and λ-interferon production are unknown. 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 α-, β- and λ-interferons in BECs and peripheral blood mononuclear cells (PBMCs) by reverse transferase-polymerase chain reaction and enzyme-linked immunosorbent assay. Rhinovirus infection of BEAS-2B BECs induced interferon-α mRNA expression transiently at 8 h and interferon-β later at 24 h while induction of interferon-λ was strongly induced at both time points. At 24 h, interferon-α protein was not detected, interferon-β was weakly induced while interferon-λ 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-α, interferon-β and interferon-λ mRNAs were all strongly induced by rhinovirus at both 8 and 24 h and proteins were induced: interferon-α>-β>-λ. Thus respiratory viruses induced expression of α-, β- and λ-interferons in BECs and PBMCs. In PBMCs interferon-α>-β>-λ while in BECs, interferon-λ>-β>-α. We conclude that interferon-λs are likely the principal interferons produced during innate responses to respiratory viruses in BECs and interferon-αs in PBMCs, while interferon-β is produced by both cell types.