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

Title: The role of IL-15 deficiency in the pathogenesis of virus-induced asthma exacerbations
Authors: Laza-Stanca, V
Message, SD
Edwards, MR
Parker, HL
Zdrenghea, MT
Kebadze, T
Kon, OM
Mallia, P
Stanciu, LA
Johnston, SL
Item Type: Journal Article
Abstract: 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.
Issue Date: 1-Jul-2011
Date of Acceptance: 26-Apr-2011
URI: http://hdl.handle.net/10044/1/43364
DOI: https://dx.doi.org/10.1371/journal.ppat.1002114
ISSN: 1553-7366
Publisher: Public Library of Science
Journal / Book Title: PLOS Pathogens
Volume: 7
Issue: 7
Copyright Statement: © 2011 Laza-Stanca et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Sponsor/Funder: Medical Research Council (MRC)
Asthma UK
Medical Research Council (MRC)
Funder's Grant Number: G0601236
RF07/04
G1000758
Keywords: Science & Technology
Life Sciences & Biomedicine
Microbiology
Parasitology
Virology
MICROBIOLOGY
PARASITOLOGY
VIROLOGY
NF-KAPPA-B
BRONCHIAL EPITHELIAL-CELLS
GENE-EXPRESSION
TRANSCRIPTION FACTORS
INTERFERON-GAMMA
DENDRITIC CELLS
MONOCYTIC CELLS
UP-REGULATION
IRF FAMILY
RHINOVIRUS
Asthma
Female
HeLa Cells
Humans
Interferon-alpha
Interferon-beta
Interleukin-15
Macrophages, Alveolar
Male
NF-kappa B
Picornaviridae Infections
Rhinovirus
Viral Load
Hela Cells
0605 Microbiology
1107 Immunology
1108 Medical Microbiology
Publication Status: Published
Article Number: ARTN e1002114
Appears in Collections:National Heart and Lung Institute
Faculty of Medicine



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