Bacterial&amp;ndash;viral load and the immune response in stable and exacerbated COPD: significance and therapeutic prospects

D’Anna, Silvestro Ennio; Balbi, Bruno; Cappello, Francesco; Carone, Mauro; Stefano, Antonino Di

doi:10.2147/copd.s93398

Cited by 32 publications

(41 citation statements)

References 60 publications

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“…This finding suggests that in stable disease the microbiota may not be directly related to the classical COPD inflammatory response developing in the bronchial mucosa. This seems to be in contrast to the situation during COPD exacerbations where a concomitant increase of bronchial inflammation [37], microbiota load [38] and TLR4 expression [39] has been observed. However, a comprehensive study of pathogen-related bacteria and related inflammatory response in bronchial biopsies of exacerbated COPD patients is lacking.…”

Section: Discussioncontrasting

confidence: 82%

Bronchial inflammation and bacterial load in stable COPD is associated with TLR4 overexpression

Stefano

Ricciardolo

Caramori³

et al. 2017

Eur Respir J

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Toll-like receptors (TLRs) and nucleotide-binding oligomerisation domain (NOD)-like receptors (NLRs) are two major forms of innate immune sensors but their role in the immunopathology of stable chronic obstructive pulmonary disease (COPD) is incompletely studied. Our objective here was to investigate TLR and NLR signalling pathways in the bronchial mucosa in stable COPD.Using immunohistochemistry, the expression levels of TLR2, TLR4, TLR9, NOD1, NOD2, CD14, myeloid differentiation primary response gene 88 (MyD88), Toll-interleukin-1 receptor domain-containing adaptor protein (TIRAP), and the interleukin-1 receptor-associated kinases phospho-IRAK1 and IRAK4 were measured in the bronchial mucosa of subjects with stable COPD of different severity (n=34), control smokers (n=12) and nonsmokers (n=12). The bronchial bacterial load of ,, and was measured by quantitative real-time PCR.TLR4 and NOD1 expression was increased in the bronchial mucosa of patients with severe/very severe stable COPD compared with control subjects. TLR4 bronchial epithelial expression correlated positively with CD4 and CD8 cells and airflow obstruction. NOD1 expression correlated with CD8 cells. The bronchial load of was directly correlated, but inversely correlated, with the degree of airflow obstruction. Bacterial load did not correlate with inflammatory cells.Bronchial epithelial overexpression of TLR4 and NOD1 in severe/very severe stable COPD, associated with increased bronchial inflammation and bacterial load, may play a role in the pathogenesis of COPD.

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Section: Discussioncontrasting

confidence: 82%

Bronchial inflammation and bacterial load in stable COPD is associated with TLR4 overexpression

Stefano

Ricciardolo

Caramori³

et al. 2017

Eur Respir J

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“…Others have found a higher phage abundance in patients with severe COPD when compared with moderate COPD and healthy controls, in line with the hypothesis of a state of dysbiosis that increases with disease progression 25 . In COPD patients, viral infections have been suggested to trigger bacterial overgrowth and infections 34,35 , demonstrating the significance of viral-bacterial interactions. Moreover, hypothetically, bacteriophages play a role in the horizontal gene transfer of bacterial virulence factors.…”

Section: Discussionmentioning

confidence: 99%

The respiratory virome and exacerbations in patients with chronic obstructive pulmonary disease

Rijn

Boheemen

Carbo

et al. 2019

Preprint

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Introduction: Exacerbations are major contributors to morbidity and mortality in patients with chronic obstructive pulmonary disease (COPD), and respiratory bacterial and viral infections are an important trigger for the occurrence of such exacerbations. However, using conventional diagnostic techniques, a causative agent is not always found. Metagenomic next-generation sequencing (mNGS) allows analysis of the complete virome, but has not yet been applied in COPD exacerbations. Objectives: To study the respiratory virome in nasopharyngeal samples during COPD exacerbations using mNGS. Study design: 88 nasopharyngeal swabs from 63 patients from the Bergen COPD Exacerbation Study (2006-2010) were analysed by mNGS and in-house qPCR for respiratory viruses. Both DNA and RNA were sequenced simultaneously using an Illumina library preparation protocol with in-house adaptations. Results: By mNGS, 23/88 samples tested positive. Sensitivity and specificity were both 96% for diagnostic targets (23/24 and 1067/1120, respectively). Viral pathogens only detected by mNGS were herpes simplex virus type 1 and coronavirus OC43. A positive correlation was found between Cq value and mNGS viral species reads (p=0.008). Patients with viral pathogens had lower percentages of bacteriophages (p<0.000). No correlation was found between viral reads (species and genus level) and clinical markers. Conclusions: The mNGS protocol used was highly sensitive and specific for semi-quantitative detection of respiratory viruses. Excellent negative predictive value implicates the power of mNGS to exclude any infectious cause in one test, with consequences for clinical decision making. Reduced abundance of bacteriophages in COPD patients with viral pathogens implicates skewing of the virome, and speculatively the bacterial population, during infection.

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“…The long-term use of antibiotics could reduce bacterial load in the airway. 86 Besides their antimicrobial effects, certain antibiotics are now known to have immune-modulatory effects on airway remodeling and have been attracting increasing research interest.…”

Section: Adaptive Immune Cells In Copdmentioning

confidence: 99%

<p>How Do Innate Immune Cells Contribute to Airway Remodeling in COPD Progression?</p>

Bu¹,

Wang²,

Yin³

2020

COPD

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Recently, the therapeutic potential of immune-modulation during the progression of chronic obstructive pulmonary disease (COPD) has been attracting increasing interest. However, chronic inflammatory response has been oversimplified in descriptions of the mechanism of COPD progression. As a form of first-line airway defense, epithelial cells exhibit phenotypic alteration, and participate in epithelial layer disorganization, mucus hypersecretion, and extracellular matrix deposition. Dendritic cells (DCs) exhibit attenuated antigen-presenting capacity in patients with advanced COPD. Immature DCs migrate into small airways, where they promote a pro-inflammatory microenvironment and bacterial colonization. In response to damageassociated molecular patterns (DAMPs) in lung tissue affected by COPD, neutrophils are excessively recruited and activated, where they promote a proteolytic microenvironment and fibrotic repair in small airways. Macrophages exhibit decreased phagocytosis in the large airways, while they demonstrate high pro-inflammatory potential in the small airways, and mediate alveolar destruction and chronic airway inflammation. Natural killer T (NKT) cells, eosinophils, and mast cells also play supplementary roles in COPD progression; however, their cellular activities are not yet entirely clear. Overall, during COPD progression, "exhausted" innate immune responses can be observed in the large airways. On the other hand, the innate immune response is enhanced in the small airways. Approaches that inhibit the inflammatory cascade, chemotaxis, or the activation of inflammatory cells could possibly delay the progression of airway remodeling in COPD, and may thus have potential clinical significance.

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Bacterial–viral load and the immune response in stable and exacerbated COPD: significance and therapeutic prospects

Cited by 32 publications

References 60 publications

Bronchial inflammation and bacterial load in stable COPD is associated with TLR4 overexpression

Bronchial inflammation and bacterial load in stable COPD is associated with TLR4 overexpression

The respiratory virome and exacerbations in patients with chronic obstructive pulmonary disease

<p>How Do Innate Immune Cells Contribute to Airway Remodeling in COPD Progression?</p>

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