The role of IL-15 deficiency in the pathogenesis of virus-induced asthma exacerbations
Author(s)
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.
Date Issued
2011-07-01
Date Acceptance
2011-04-26
Citation
PLOS Pathogens, 2011, 7 (7)
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
Medical Research Council (MRC)
Asthma UK
Medical Research Council (MRC)
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000293339300011&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Grant Number
G0601236
RF07/04
G1000758
Subjects
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