The Role of IL-15 Deficiency in the Pathogenesis of Virus-Induced Asthma Exacerbations

PLoS Pathogens

Simon D. Message¹  Hayley L. Parker¹  Tatiana Kebadze¹  Luminita A. Stanciu¹  Vasile Laza-Stanca¹  Mihnea T. Zdrenghea¹  Onn M. Kon¹  Sebastian L. Johnston²  Michael R. Edwards²  Patrick Mallia² 

[1] Department of Respiratory Medicine, National Heart and Lung Institute, MRC & Asthma UK Centre in Allergic Mechanisms of Asthma, Centre for Respiratory Infection, Imperial College London, London, United Kingdom;Imperial College Healthcare NHS Trust, London, United Kingdom

关键词: Asthma;    Macrophages;    Rhinovirus infection;    Respiratory infections;    Transcription factors;    Antiviral immune response;    Immune deficiency;    Alveolar macrophages;   

DOI  :  10.1371/journal.ppat.1002114

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Rhinovirus infections are the major cause of asthma exacerbations. We hypothesised that IL-15, a cytokine implicated in innate and acquired antiviral immunity, may be deficient in asthma and important in the pathogenesis of asthma exacerbations. We investigated regulation of IL-15 induction by rhinovirus in human macrophages in vitro, IL-15 levels in bronchoalveolar lavage (BAL) fluid and IL-15 induction by rhinovirus in BAL macrophages from asthmatic and control subjects, and related these to outcomes of infection in vivo. Rhinovirus induced IL-15 in macrophages was replication-, NF-κB- and α/β interferon-dependent. BAL macrophage IL-15 induction by rhinovirus was impaired in asthmatics and inversely related to lower respiratory symptom severity during experimental rhinovirus infection. IL-15 levels in BAL fluid were also decreased in asthmatics and inversely related with airway hyperresponsiveness and with virus load during in vivo rhinovirus infection. Deficient IL-15 production in asthma may be important in the pathogenesis of asthma exacerbations.

【 授权许可】

CC BY