Respiratory virus induction of alpha-, beta- and lambda-interferons in bronchial epithelial cells and peripheral blood mononuclear cells.
BACKGROUND
Respiratory viruses, predominantly rhinoviruses are the major cause of asthma exacerbations. Impaired production of interferon-beta in rhinovirus infected bronchial epithelial cells (BECs) and of the newly discovered interferon-lambdas 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 alpha-, beta- and lambda-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 alpha-, beta- and lambda-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-alpha mRNA expression transiently at 8 h and interferon-beta later at 24 h while induction of interferon-lambda was strongly induced at both time points. At 24 h, interferon-alpha protein was not detected, interferon-beta was weakly induced while interferon-lambda 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-alpha, interferon-beta and interferon-lambda mRNAs were all strongly induced by rhinovirus at both 8 and 24 h and proteins were induced: interferon-alpha>-beta>-lambda. Thus respiratory viruses induced expression of alpha-, beta- and lambda-interferons in BECs and PBMCs. In PBMCs interferon-alpha>-beta>-lambda while in BECs, interferon-lambda>-beta>-alpha.


CONCLUSIONS
We conclude that interferon-lambdas are likely the principal interferons produced during innate responses to respiratory viruses in BECs and interferon-alphas in PBMCs, while interferon-beta is produced by both cell types.
Khaitov
M R
MR
Department of Respiratory Medicine, National Heart and Lung Institute, Wright Fleming Institute of Infection and Immunity and MRC and Asthma UK Centre in Allergic Mechanisms of Asthma, Imperial College London, Norfolk Place, London, UK.
Laza-Stanca
V
V
Edwards
M R
MR
Walton
R P
RP
Rohde
G
G
Contoli
M
M
Papi
A
A
Stanciu
L A
LA
Kotenko
S V
SV
Johnston
S L
SL
D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D009980:Influenza A virus / Q000276:immunology; D016898:Interferon-alpha / Q000096:biosynthesis*; D016899:Interferon-beta / Q000096:biosynthesis*; D007372:Interferons / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D012333:RNA, Messenger / Q000032:analysis; D020545:Respiratory Mucosa / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012229:Rhinovirus / Q000276:immunology*
D016898:Interferon-alpha; D012333:RNA, Messenger; D016899:Interferon-beta; D007372:Interferons