Rhinovirus 16-induced IFN-α and IFN-β are deficient in bronchoalveolar lavage cells in asthmatic patients.
BACKGROUND
Asthmatic patients have defective rhinovirus-induced IFN-β and IFN-λ production from bronchial epithelial cells and IFN-λ from bronchoalveolar lavage (BAL) cells. Whether bronchoalveolar lavage cells have defective type I interferon responses to rhinovirus is unknown, as are mechanisms explaining defective rhinovirus interferon induction in asthmatic patients.


OBJECTIVE
We sought to investigate rhinovirus induction of type I interferons in BAL and blood mononuclear cells from asthmatic patients and healthy subjects and to investigate mechanisms of any deficiency observed.


METHODS
BAL and blood mononuclear cells from atopic asthmatic patients and healthy subjects were infected with rhinovirus ex vivo. Interferon proteins were analyzed by using ELISA. mRNA expression of key components of interferon induction pathways were analyzed by using quantitative PCR.


RESULTS
Rhinovirus induction of type I interferon protein was delayed and deficient in BAL cells from asthmatic patients, and lower interferon levels were associated with greater airway hyperresponsiveness and skin prick test response positivity. Expression of Toll-like receptor (TLR) 3, TLR7, TLR8, retinoic acid-inducible gene I (RIG-I), melanoma differentiation-associated gene 5 (MDA-5), TIR domain-containing adapter-inducing IFN-β (TRIF), myeloid differentiation primary response gene 88 (MyD88), caspase recruitment domain adaptor inducing IFN-β (CARDIF), IL-1 receptor-associated kinase 4 (IRAK4), IκB kinase β (IKKB), IκB kinase ι (IKKI), interferon regulatory factors 3 and 7, and rhinovirus induction of expression of the virus-inducible molecules TLR3, TLR7, RIG-I, and MDA-5 were not impaired in these interferon-deficient BAL cells in asthmatic patients. Defective rhinovirus interferon induction was not observed in blood mononuclear cells.


CONCLUSIONS
Rhinovirus induction of type I interferons in BAL cells is delayed and deficient and might be a marker of more severe asthma. Defective rhinovirus interferon induction in asthmatic patients was not accompanied by differences in the expression or induction of key molecules implicated in viral induction of interferons.
National Heart & Lung Institute, Imperial College London, London, United Kingdom. annemarie.sykes@imperial.ac.uk
Annemarie
A
Sykes
Michael R
MR
Edwards
Jonathan
J
Macintyre
Ajerico
A
del Rosario
Eteri
E
Bakhsoliani
Maria-Belen
MB
Trujillo-Torralbo
Onn Min
OM
Kon
Patrick
P
Mallia
Mark
M
McHale
Sebastian L
SL
Johnston
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000328:Adult; D001249:Asthma / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D001992:Bronchoalveolar Lavage Fluid; D016022:Case-Control Studies; D004847:Epithelial Cells / Q000378:metabolism / Q000821:virology; D005260:Female; D006801:Humans; D016898:Interferon-alpha / Q000096:biosynthesis*; D016899:Interferon-beta / Q000096:biosynthesis*; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000821:virology; D008297:Male; D020365:RNA Helicases / Q000378:metabolism; D051192:Receptors, Pattern Recognition / Q000235:genetics / Q000378:metabolism; D012229:Rhinovirus / Q000276:immunology*; D015398:Signal Transduction; D012882:Skin Tests; D013997:Time Factors; D051196:Toll-Like Receptor 3 / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D016898:Interferon-alpha; D051192:Receptors, Pattern Recognition; D051196:Toll-Like Receptor 3; D014157:Transcription Factors; D016899:Interferon-beta; D020365:RNA Helicases