Rhinovirus Infection Induces Degradation of Antimicrobial Peptides and Secondary Bacterial Infection in Chronic Obstructive Pulmonary Disease
Patrick Mallia,Joseph Footitt,Rosa Sotero,Annette Jepson,Marco Contoli,Maria-Belen Trujillo-Torralbo,Tatiana Kebadze,Julia Aniscenko,Gregory Oleszkiewicz,Katrina Gray,Simon D. Message,Kazuhiro Ito,Peter J. Barnes,Ian M. Adcock,Alberto Papi,Luminita A. Stanciu,Sarah L. Elkin,Onn Min Kon,Malcolm Johnson,Sebastian L. Johnston +19 more
Reads0
Chats0
TLDR
Rinovirus infections are frequently followed by secondary bacterial infections in COPD and cleavage of the antimicrobial peptides SLPI and elafin by virus-induced neutrophil elastase may precipitate these secondaryacterial infections.Abstract:
Rationale: Chronic obstructive pulmonary disease (COPD) exacerbations are associated with virus (mostly rhinovirus) and bacterial infections, but it is not known whether rhinovirus infections precipitate secondary bacterial infections.
Objectives: To investigate relationships between rhinovirus infection and bacterial infection and the role of antimicrobial peptides in COPD exacerbations.
Methods: We infected subjects with moderate COPD and smokers and nonsmokers with normal lung function with rhinovirus. Induced sputum was collected before and repeatedly after rhinovirus infection and virus and bacterial loads measured with quantitative polymerase chain reaction and culture. The antimicrobial peptides secretory leukoprotease inhibitor (SLPI), elafin, pentraxin, LL-37, α-defensins and β-defensin-2, and the protease neutrophil elastase were measured in sputum supernatants.
Measurements and Main Results: After rhinovirus infection, secondary bacterial infection was detected in 60% of subjects with COPD, 9.5% of smokers, and 10% of nonsmokers (P < 0.001). Sputum virus load peaked on Days 5–9 and bacterial load on Day 15. Sputum neutrophil elastase was significantly increased and SLPI and elafin significantly reduced after rhinovirus infection exclusively in subjects with COPD with secondary bacterial infections, and SLPI and elafin levels correlated inversely with bacterial load.
Conclusions: Rhinovirus infections are frequently followed by secondary bacterial infections in COPD and cleavage of the antimicrobial peptides SLPI and elafin by virus-induced neutrophil elastase may precipitate these secondary bacterial infections. Therapy targeting neutrophil elastase or enhancing innate immunity may be useful novel therapies for prevention of secondary bacterial infections in virus-induced COPD exacerbations.read more
Citations
More filters
Journal ArticleDOI
Antimicrobial host defence peptides: functions and clinical potential
TL;DR: The emerging potential to therapeutically harness cationic host defence peptides to treat infectious diseases, chronic inflammatory disorders and wound healing is assessed, highlighting current preclinical studies and clinical trials.
Journal ArticleDOI
Outgrowth of the Bacterial Airway Microbiome after Rhinovirus Exacerbation of Chronic Obstructive Pulmonary Disease
Philip L. Molyneaux,Patrick Mallia,Michael J. Cox,Joseph Footitt,Saffron A.G. Willis-Owen,Daniel Homola,Maria-Belen Trujillo-Torralbo,Sarah L. Elkin,Onn Min Kon,William O.C.M. Cookson,Miriam F. Moffatt,Sebastian L. Johnston +11 more
TL;DR: It is suggested that rhinovirus infection in COPD alters the respiratory microbiome and may precipitate secondary bacterial infections.
Journal ArticleDOI
Host–microorganism interactions in lung diseases
TL;DR: It is proposed that akin to recent discoveries in intestinal research, dysbiosis of the airway microbiota could underlie susceptibility to, and progression and chronicity of lung disease.
Journal ArticleDOI
Long-term IL-33-producing epithelial progenitor cells in chronic obstructive lung disease
Derek E. Byers,Jennifer Alexander-Brett,Anand C. Patel,Eugene Agapov,Geoffrey Dang-Vu,Xiaohua Jin,Kangyun Wu,Yingjian You,Yael G. Alevy,Jean-Phillippe Girard,Thaddeus S. Stappenbeck,G. Alexander Patterson,Richard A. Pierce,Steven L. Brody,Michael J. Holtzman +14 more
TL;DR: It is demonstrated here that lung levels of IL-33 are selectively increased in postviral mice with chronic obstructive lung disease and in humans with very severe Chronic obstructive pulmonary disease (COPD).
Journal ArticleDOI
Antiviral Mechanisms of Human Defensins
TL;DR: The antiviral activity ofdefensins is well established as are the variety of mechanisms by which defensins achieve this inhibition; however, additional research is needed to fully understand the role of defensin in viral pathogenesis.
References
More filters
Journal ArticleDOI
Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary.
Jørgen Vestbo,Suzanne S. Hurd,Alvar Agusti,Paul W. Jones,Claus Vogelmeier,Antonio Anzueto,Peter J. Barnes,Leonardo M. Fabbri,Fernando J. Martinez,Masaharu Nishimura,Robert A. Stockley,Don D. Sin,Roberto Rodriguez-Roisin +12 more
TL;DR: It is recommended that spirometry is required for the clinical diagnosis of COPD to avoid misdiagnosis and to ensure proper evaluation of severity of airflow limitation.
Journal ArticleDOI
Projections of Global Mortality and Burden of Disease from 2002 to 2030
Colin Mathers,Dejan Loncar +1 more
TL;DR: These projections represent a set of three visions of the future for population health, based on certain explicit assumptions, which enable us to appreciate better the implications for health and health policy of currently observed trends, and the likely impact of fairly certain future trends.
Journal ArticleDOI
Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. NHLBI/WHO Global Initiative for Chronic Obstructive Lung Disease (GOLD) Workshop summary.
TL;DR: List of participants (GOLD Scientific Committee): Nicholas Anthonisen, Winnipeg, Canada, William C. Bailey, Birmingham, US, Tim Clark, London, UK, Leonardo Fabbri, Modena, Italy, Yoshinosuke Fukuchi, Tokyo, Japan; Lawrence Grouse, Seattle, US; James C. Hogg, Vancouver, Canada; Dirkje S. Postma, Groningen, the Netherlands.
Journal ArticleDOI
Susceptibility to Exacerbation in Chronic Obstructive Pulmonary Disease
John R. Hurst,Jørgen Vestbo,Jørgen Vestbo,Antonio Anzueto,Nicholas Locantore,Hana Müllerová,Ruth Tal-Singer,Bruce E. Miller,David A. Lomas,Alvar Agusti,William MacNee,Peter M.A. Calverley,Stephen I. Rennard,Emiel F.M. Wouters,Jadwiga A. Wedzicha +14 more
TL;DR: Although exacerbations become more frequent and more severe as COPD progresses, the rate at which they occur appears to reflect an independent susceptibility phenotype, which has implications for the targeting of exacerbation-prevention strategies across the spectrum of disease severity.
Journal ArticleDOI
Effect of exacerbation on quality of life in patients with chronic obstructive pulmonary disease.
Terence A. R. Seemungal,Gavin C. Donaldson,E.A. Paul,Janine C Bestall,Donald J. Jeffries,Jadwiga A. Wedzicha +5 more
TL;DR: It is suggested that patient quality of life is related to COPD exacerbation frequency and factors predictive of frequent exacerbations were daily cough, daily wheeze, and daily cough and sputum.
Related Papers (5)
Infection in the Pathogenesis and Course of Chronic Obstructive Pulmonary Disease
Sanjay Sethi,Timothy F. Murphy +1 more