Rhinovirus 16ainduced IFN- alpha and IFN- beta are deficient in bronchoalveolar lavage cells in asthmatic patients

Background: Asthmatic patients have defective rhinovirus-induced IFN- beta and IFN- alpha production from bronchial epithelial cells and IFN- alpha 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 acidainducible gene I (RIG-I), melanoma differentiationaassociated gene 5 (MDA-5), TIR domainacontaining adapter-inducing IFN- beta (TRIF), myeloid differentiation primary response gene 88 (MyD88), caspase recruitment domain adaptor inducing IFN- beta (CARDIF), IL-1 receptoraassociated kinase 4 (IRAK4), I Kappa B kinase beta (IKKB), I Kappa B kinase I1 (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.