Airway Inflammation and Bronchial Bacterial Colonization in Chronic Obstructive Pulmonary Disease

Sethi, Sanjay; Maloney, Jane; Grove, Lori; Wrona, Catherine; Berenson, Charles S.

doi:10.1164/rccm.200509-1525oc

Cited by 328 publications

(244 citation statements)

References 36 publications

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“…NTHI infection has been associated with the initiation of inflammatory exacerbations of COPD (34)(35)(36)(37). Our work shows that in an elastase-treated mouse lung, which mirrors the pathology of a COPD lung, parental strain NTHI survives better than in an untreated lung infection.…”

Section: Discussionmentioning

confidence: 69%

Peroxiredoxin-Glutaredoxin and Catalase Promote Resistance of Nontypeable Haemophilus influenzae 86-028NP to Oxidants and Survival within Neutrophil Extracellular Traps

et al. 2015

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Nontypeable Haemophilus influenzae (NTHI) is a common commensal and opportunistic pathogen of the human airways. For example, NTHI is a leading cause of otitis media and is the most common cause of airway infections associated with chronic obstructive pulmonary disease (COPD). These infections are often chronic/recurrent in nature and involve bacterial persistence within biofilm communities that are highly resistant to host clearance. Our previous work has shown that NTHI within biofilms has increased expression of factors associated with oxidative stress responses. The goal of this study was to define the roles of catalase (encoded by hktE) and a bifunctional peroxiredoxin-glutaredoxin (encoded by pdgX) in resistance of NTHI to oxidants and persistence in vivo. Isogenic NTHI strain 86-028NP mutants lacking hktE and pdgX had increased susceptibility to peroxide. Moreover, these strains had persistence defects in the chinchilla infection model for otitis media, as well as in a murine model for COPD. Additional work showed that pdgX and hktE were important determinants of NTHI survival within neutrophil extracellular traps (NETs), which we have shown to be an integral part of NTHI biofilms in vivo. Based on these data, we conclude that catalase and peroxiredoxin-glutaredoxin are determinants of bacterial persistence during chronic/recurrent NTHI infections that promote bacterial survival within NETs. Nontypeable Haemophilus influenzae (NTHI) is a common resident of the human upper airways, where carriage is usually asymptomatic (1). In patients with mucociliary clearance deficits, NTHI can also cause opportunistic infections; these include airway infections in patients with chronic obstructive pulmonary disease (COPD) (2) and otitis media infections in children (3). These infections are often chronic and recurrent in nature, and it is now well established that the persistent NTHI populations reside within biofilm communities on the airway surface (4-6). NTHI persists in the chinchilla middle ear even in the face of immune effectors that contribute to the biofilm structure, such as neutrophils and neutrophil extracellular traps (NETs) (7). These NETs can have phagocytosis-independent antimicrobial activity that involves trapping of invading microorganisms by decondensed chromatin and microbicides from the neutrophil granules, which decorate the DNA NET lattice (8, 9). Our recent work shows that NTHI bacteria survive within NETs (7) and are resistant to extracellular killing within the NET and phagocytic killing by incoming neutrophils (10).The objective of the present study was to test the relevance of peroxiredoxin-glutaredoxin (encoded by pdgX) and catalase (encoded by hktE) in opportunistic infections caused by NTHI strain 86-028NP. The data support the conclusion that these factors have overlapping roles in resistance of NTHI to oxidative killing and thus promote survival of NTHI within NET structures and persistence in vivo in the lung and middle ear. MATERIALS AND METHODSBacterial culture and manipulation. A ...

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Section: Discussionmentioning

confidence: 69%

Peroxiredoxin-Glutaredoxin and Catalase Promote Resistance of Nontypeable Haemophilus influenzae 86-028NP to Oxidants and Survival within Neutrophil Extracellular Traps

et al. 2015

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“…One example is the association between hepatitis B and C virus and the incidence of hepatocellular carcinoma [74]. In smokers, the establishment of chronic microbial colonisation in the lungs is seen, even in the absence of airway obstruction, and this persists in ex-smokers with COPD [75]. Unlike the sterile lungs of a healthy individual, we know that there is a failure of the innate immune system in COPD.…”

Section: The Role Of Inflammationmentioning

confidence: 99%

The Epithelial Cell and Lung Cancer: The Link between Chronic Obstructive Pulmonary Disease and Lung Cancer

Rooney

Sethi

2011

Respiration

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Chronic obstructive pulmonary disease (COPD) and lung cancer currently form the basis for an enormous disease burden in the developed world. As a result of changing smoking trends and tobacco use, regrettably, a similar picture is arising rapidly within the developing world. COPD is a recognised risk factor for lung cancer, and a significant proportion of patients diagnosed with lung cancer have COPD. An association between both conditions has long been suspected but has proven difficult to demonstrate thus far. However, the common factors between both conditions are now becoming apparent thanks to recent clinical and molecular advances. Abnormal regulation of the immune system and the establishment of chronic inflammation appear to be key events in this process. In addition, the complex interplay between genes and environment and the possibility of a genetic basis to lung cancer susceptibility in the context of COPD are becoming clearer concepts. As we begin to unravel the common pathways and molecules in the pathogenesis of both conditions, we may be able to not only identify novel strategies to prevent and treat COPD and lung cancer, but also recognise molecular markers to identify patients at high risk of developing lung cancer.

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“…Lungs of COPD patients are often colonized or infected with Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pneumonia, and Pseudomonas aeruginosa (Murphy et al, 2004;Sethi et al, 2006). Culture-independent approaches showed that the microbiome of the COPD lung differs significantly from the microbiome of healthy lungs (Erb-Downward et al, 2011;Sze et al, 2012;Zakharkina et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Combined exposure to bacteria and cigarette smoke resembles characteristic phenotypes of human COPD in a murine disease model

Herr

Han

Dong

et al. 2015

Experimental and Toxicologic Pathology

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Airway Inflammation and Bronchial Bacterial Colonization in Chronic Obstructive Pulmonary Disease

Abstract: Bacterial colonization is associated with neutrophilic airway lumen inflammation in ex-smokers with COPD and could contribute to progression of airway disease in COPD.

Cited by 328 publications

References 36 publications

Peroxiredoxin-Glutaredoxin and Catalase Promote Resistance of Nontypeable Haemophilus influenzae 86-028NP to Oxidants and Survival within Neutrophil Extracellular Traps

Peroxiredoxin-Glutaredoxin and Catalase Promote Resistance of Nontypeable Haemophilus influenzae 86-028NP to Oxidants and Survival within Neutrophil Extracellular Traps

The Epithelial Cell and Lung Cancer: The Link between Chronic Obstructive Pulmonary Disease and Lung Cancer

Combined exposure to bacteria and cigarette smoke resembles characteristic phenotypes of human COPD in a murine disease model

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