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

• Published in: PLoS pathogens Vol. 7; no. 7; p. e1002114
• Main Authors: Laza-Stanca, Vasile, Message, Simon D., Edwards, Michael R., Parker, Hayley L., Zdrenghea, Mihnea T., Kebadze, Tatiana, Kon, Onn M., Mallia, Patrick, Stanciu, Luminita A., Johnston, Sebastian L.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.07.2011; Public Library of Science (PLoS)
• Subjects: Asthma; Asthma - immunology; Asthma - pathology; Asthma - virology; Biomedical research; Experiments; Female; Gene expression; Grants; Health aspects; HeLa Cells; Humans; Immune system; Immunology; Infections; Interferon; Interferon-alpha - immunology; Interferon-beta - immunology; Interleukin-15; Interleukins; Macrophages; Macrophages, Alveolar - immunology; Macrophages, Alveolar - pathology; Macrophages, Alveolar - virology; Male; Medical research; Medicine; Molecular weight; NF-kappa B - immunology; Pathogenesis; Physiological aspects; Picornaviridae Infections - immunology; Picornaviridae Infections - pathology; Rhinovirus - immunology; Rhinoviruses; Risk factors; Viral Load - immunology; United Kingdom
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1002114

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.