Rhinovirus-induced lower respiratory illness is increased in asthma and related to virus load and Th1/2 cytokine and IL-10 production.
Simon D. Message,Vasile Laza-Stanca,Patrick Mallia,Hayley L. Parker,Jie Zhu,Tatiana Kebadze,Marco Contoli,Gwen Sanderson,Onn Min Kon,Alberto Papi,Peter K. Jeffery,Luminita A. Stanciu,Sebastian L. Johnston +12 more
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Increased RV-induced clinical illness severity in asthmatic compared with normal subjects is demonstrated, evidence of strong relationships between virus load, lower airway virus-induced inflammation and asthma exacerbation severity is provided, and indicates augmented Th2 or impaired Th1 or IL-10 immunity are likely important mechanisms.Abstract:
Acute exacerbations are the major cause of asthma morbidity, mortality, and health-care costs and are difficult to treat and prevent. The majority of asthma exacerbations are associated with rhinovirus (RV) infection, but evidence supporting a causal relationship is weak and mechanisms are poorly understood. We hypothesized that in asthmatic, but not normal, subjects RV infection would induce clinical, physiologic, and pathologic lower airway responses typical of an asthma exacerbation and that these changes would be related to virus replication and impaired T helper 1 (Th1)/IL-10 or augmented Th2 immune responses. We investigated physiologic, virologic, and immunopathologic responses to experimental RV infection in blood, induced sputum, and bronchial lavage in 10 asthmatic and 15 normal volunteers. RV infection induced significantly greater lower respiratory symptoms and lung function impairment and increases in bronchial hyperreactivity and eosinophilic lower airway inflammation in asthmatic compared with normal subjects. In asthmatic, but not normal, subjects virus load was significantly related to lower respiratory symptoms, bronchial hyperreactivity, and reductions in blood total and CD8+ lymphocytes; lung function impairment was significantly related to neutrophilic and eosinophilic lower airway inflammation. The same virologic and clinical outcomes were strongly related to deficient IFN-γ and IL-10 responses and to augmented IL-4, IL-5, and IL-13 responses. This study demonstrates increased RV-induced clinical illness severity in asthmatic compared with normal subjects, provides evidence of strong relationships between virus load, lower airway virus-induced inflammation and asthma exacerbation severity, and indicates augmented Th2 or impaired Th1 or IL-10 immunity are likely important mechanisms.read more
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Journal ArticleDOI
Innate IFNs and Plasmacytoid Dendritic Cells Constrain Th2 Cytokine Responses to Rhinovirus: A Regulatory Mechanism with Relevance to Asthma
Antonia L. Pritchard,Melanie L. Carroll,Julie G. Burel,Olivia J. White,Simon Phipps,John W. Upham +5 more
TL;DR: This study sought to examine normal homeostatic mechanisms regulating adaptive immunity to RV in healthy humans, focusing on effects of IFN-αβ and plasmacytoid dendritic cells (pDC) on Th2 immune responses.
Journal ArticleDOI
The Role of IL-15 Deficiency in the Pathogenesis of Virus-Induced Asthma Exacerbations
Vasile Laza-Stanca,Simon D. Message,Simon D. Message,Michael R. Edwards,Hayley L. Parker,Mihnea Zdrenghea,Tatiana Kebadze,Onn Min Kon,Patrick Mallia,Patrick Mallia,Luminita A. Stanciu,Sebastian L. Johnston,Sebastian L. Johnston +12 more
TL;DR: IL-15 levels in BAL fluid were decreased in asthmatics and inversely related with airway hyperresponsiveness and with virus load during in vivo rhinovirus infection, suggesting deficient IL-15 production in asthma may be important in the pathogenesis of asthma exacerbations.
Journal ArticleDOI
Human rhinovirus proteinase 2A induces TH1 and TH2 immunity in patients with chronic obstructive pulmonary disease
Manisha Singh,Seung-Hyo Lee,Paul Porter,Chuang Xu,Ayako Ohno,Robert L. Atmar,Stephen B. Greenberg,Venkata Bandi,James E. Gern,S. P. Amineva,Alex Aminev,Tim Skern,Pamela Smithwick,Sarah Perusich,Nadia Barrow,Luz Roberts,David B. Corry,Farrah Kheradmand +17 more
TL;DR: The findings suggest that patients with severe COPD show TH1- and TH2-biased responses during AE-COPD, and HRV-encoded proteinase 2A, like other microbial proteinases, could provide a TH1 andTH2-biasing adjuvant factor during upper and lower respiratory tract infection in patients withsevere COPD.
Journal ArticleDOI
Th2-associated immunity to bacteria in teenagers and susceptibility to asthma.
Elysia M. Hollams,Belinda J. Hales,Claus Bachert,Wouter Huvenne,Faith Parsons,N H de Klerk,Michael Serralha,Barbara J. Holt,Staffan Ahlstedt,Wayne R. Thomas,Peter D. Sly,Patrick G. Holt +11 more
TL;DR: It is theorised that type-2 immunity to S. aureus and asthma phenotypes probably reflects IgE-mediated effector cell activation via enterotoxin super antigens which are secreted in soluble form, and may reflect their lower availability in soluble forms that can crosslink IgE receptors.
References
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Sebastian L. Johnston,Philip Pattemore,G. Sanderson,Sandra Smith,F Lampe,Lynn Josephs,P. Symington,S. O'Toole,S. H. Myint,D. A. J. Tyrrell +9 more
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TL;DR: In patients who have persistent symptoms of asthma despite treatment with inhaled glucocorticoids, the addition of formoterol to budesonid therapy or the use of a higher dose of budesonide may be beneficial.
Journal ArticleDOI
Asthmatic bronchial epithelial cells have a deficient innate immune response to infection with rhinovirus
Peter A. B. Wark,Sebastian L. Johnston,Fabio Bucchieri,Robert M. Powell,Sarah M. Puddicombe,Vasile Laza-Stanca,Stephen T. Holgate,Donna E. Davies +7 more
TL;DR: A causal link between deficient interferon-β, impaired apoptosis and increased virus replication is demonstrated, suggesting a novel use for type I interferons in the treatment or prevention of virus-induced asthma exacerbations.
Journal ArticleDOI
Role of deficient type III interferon-λ production in asthma exacerbations
Marco Contoli,Simon D. Message,Vasile Laza-Stanca,Michael R. Edwards,Peter A. B. Wark,Peter A. B. Wark,Nathan W. Bartlett,Tatiana Kebadze,Patrick Mallia,Luminita A. Stanciu,Hayley L. Parker,Louise Slater,Anita Lewis-Antes,Onn Min Kon,Stephen T. Holgate,Donna E. Davies,Sergei V. Kotenko,Alberto Papi,Sebastian L. Johnston +18 more
TL;DR: In this paper, the authors show deficient induction of interferon-λs by rhinovirus in primary bronchial epithelial cells and alveolar macrophages, which was highly correlated with severity of rhinovirus induced asthma exacerbation and virus load in experimentally infected human volunteers.
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