The role of IL-15 deficiency in the pathogenesis of virus-induced asthma exacerbations

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 rhino...

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Bibliographic Details
Published in:PLoS pathogens 2011-07, Vol.7 (7), p.e1002114-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: Article
Language:English
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
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Summary: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.
ISSN:1553-7374
1553-7366
1553-7374
DOI:10.1371/journal.ppat.1002114