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

Abstract
Background: 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. 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 α‐, β‐ and λ‐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‐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. Conclusions: 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.