Rhinovirus 16-induced IFN-伪 and IFN-尾 are deficient in bronchoalveolar lavage cells in asthmatic patients

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• 作者：Annemarie Sykes ; MD ; PhD^a ; ^b ; ^c ; ^d ; ^{annemarie.sykes@imperial.ac.uk} ; Michael R. Edwards ; PhD^a ; ^b ; ^c ; Jonathan Macintyre ; MD ; BSc^a ; ^b ; ^c ; ^d ; Ajerico del Rosario ; BSc^a ; ^b ; ^c ; ^d ; Eteri Bakhsoliani ; MSc^a ; ^b ; ^c ; Maria-Belen Trujillo-Torralbo ; BSc^a ; ^b ; ^c ; ^d ; Onn Min Kon ; MD ; PhD^d ; Patrick Mallia ; MD ; PhD^a ; ^b ; ^c ; Mark McHale ; PhD^e ; Sebastian L. Johnston ; MD ; PhD^a ; ^b ; ^c ; ^d
• 关键词：Asthma ; interferon ; rhinovirus ; bronchoalveolar lavage cells ; peripheral blood mononuclear cells ; airway hyperresponsiveness
• 刊名：Journal of Allergy and Clinical Immunology
• 出版年：2012
• 期刊代码：158_00916749
• 类别：med
• 出版时间：June, 2012
• 卷：129
• 期：6
• 页码：1506-1514.e6
• 文件大小：697 K

摘要

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Background

Asthmatic patients have defective rhinovirus-induced IFN-尾 and IFN-位 production from bronchial epithelial cells and IFN-位 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聽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聽acid-inducible gene I (RIG-I), melanoma differentiation-associated gene 5 (MDA-5), TIR domain-containing adapter-inducing IFN-尾 (TRIF), myeloid differentiation primary response gene 88 (MyD88), caspase recruitment domain adaptor inducing IFN-尾 (CARDIF), IL-1 receptor-associated kinase 4 (IRAK4), I魏B kinase 尾 (IKKB), I魏B kinase 喂 (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.