ArticlePloS one2015
Impaired Innate COPD Alveolar Macrophage Responses and Toll-Like Receptor-9 Polymorphisms.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- TLR9 Rs352140 polymorphism contributes to a decreased risk of bacterial meningitis: evidence from a meta-analysis.Epidemiology and infection · 2020Pooled it
- ANT1 Deficiency Impairs Macrophage Metabolism and Migration, Protecting Against Emphysema in Chronic Obstructive Pulmonary Disease.American journal of respiratory cell and molecular biology · 2025Article
- Article
- Microbiome Modulation as a Novel Strategy to Treat and Prevent Respiratory Infections.Antibiotics (Basel, Switzerland) · 2022Review
- The Emerging Role of Macrophages in Chronic Obstructive Pulmonary Disease: The Potential Impact of Oxidative Stress and Extracellular Vesicle on Macrophage Polarization and Function.Antioxidants (Basel, Switzerland) · 2022Review
- Association of toll-like receptors polymorphisms with COPD risk in Chinese population.Frontiers in genetics · 2022Article
- Expanding role of deoxyribonucleic acid-sensing mechanism in the development of lifestyle-related diseases.Frontiers in cardiovascular medicine · 2022Review
- Hepcidin Is Essential for Alveolar Macrophage Function and Is Disrupted by Smoke in a Murine Chronic Obstructive Pulmonary Disease Model.Journal of immunology (Baltimore, Md. : 1950) · 2020Article
- Abundance of Non-Polarized Lung Macrophages with Poor Phagocytic Function in Chronic Obstructive Pulmonary Disease (COPD).Biomedicines · 2020Article
- Lung Macrophage Functional Properties in Chronic Obstructive Pulmonary Disease.International journal of molecular sciences · 2020Review
- The Interplay Between Immune Response and Bacterial Infection in COPD: Focus Upon Non-typeableFrontiers in immunology · 2018Review
- Dysregulated Functions of Lung Macrophage Populations in COPD.Journal of immunology research · 2018Review
- Influence of lung CT changes in chronic obstructive pulmonary disease (COPD) on the human lung microbiome.PloS one · 2017Article
- Post-bronchiolitis wheezing is associated with toll-like receptor 9 rs187084 gene polymorphism.Scientific reports · 2016Article
- TLR9 expression is required for the development of cigarette smoke-induced emphysema in mice.American journal of physiology. Lung cellular and molecular physiology · 2016Article
- Review
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundDysfunctional innate responses of alveolar macrophages to nontypeable Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pneumoniae contribute to morbidity in chronic obstructive pulmonary disease (COPD). Our earlier studies discovered impaired COPD alveolar macrophage responses to Toll-like receptor (TLR) ligands of nontypeable H. influenzae and provide rationale for further evaluation of TLR signaling. While the role of TLR single nucleotide polymorphisms is increasingly recognized in inflammatory diseases, TLR single nucleotide polymorphisms in COPD have only recently been explored. We hypothesized that specific TLR polymorphisms are associated with dysfunctional innate immune COPD alveolar macrophage responses and investigated polymorphisms of TLR2(Arg753Gln), TLR4(Thr399Ile; Asp299Gly), and TLR9(T1486C; T1237C).
methodsDNA was purified from cells of 1) healthy nonsmokers (n = 20); 2) COPD ex-smokers (n = 83); 3) COPD active smokers (n = 93). DNA amplifications (polymerase chain reaction) were performed for each SNP. Alveolar macrophages from each group were incubated with nontypeable H. influenzae, M. catarrhalis and S. pneumoniae. Cytokine induction of macrophage supernatants was measured and the association with TLR single nucleotide polymorphism expression was determined.
resultsNo significant inter-group differences in frequency of any TLR SNP existed. However both TLR9 single nucleotide polymorphisms were expressed in high frequency. Among COPD ex-smokers, diminished IL-8 responsiveness to nontypeable H. influenzae, M. catarrhalis and S. pneumoniae was strongly associated with carriage of TLR9(T1237C) (p = 0.02; p = 0.008; p = 0.02), but not TLR9(T1486C). Carriage of TLR9(T1237C), but not TLR9(T1486C), correlated with diminished FEV1%predicted (p = 0.037).
conclusionOur results demonstrate a notable association of TLR9(T1237C) expression with dysfunctional innate alveolar macrophage responses to respiratory pathogens and with severity of COPD.
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