Reduced Clearance of Fungal Spores by Chronic Obstructive Pulmonary Disease GM-CSF– and M-CSF–derived Macrophages

Wrench, Catherine; Belchamber, Kylie; Bercusson, Amelia; Barnes, Peter J.; Armstrong‐James, Darius; Donnelly, Louise E.

doi:10.1165/rcmb.2017-0351le

Cited by 19 publications

(13 citation statements)

References 8 publications

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“…Reduced phagocytic function of macrophages in COPD is well described, encompassing impaired phagocytosis of disease-relevant bacteria (non-typeable Haemophilus influenzae and Streptococcus pneumoniae ), fungi 81 and apoptotic neutrophils via efferocytosis 82– 84 . However, little research to date has focused on the phagocytic ability of neutrophils, and data so far provide conflicting results; some demonstrate no differences in phagocytosis 85– 87 and others suggest a reduction 88 .…”

Section: Chronic Obstructive Pulmonary Diseasementioning

confidence: 99%

Understanding the role of neutrophils in chronic inflammatory airway disease

et al. 2019

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Airway neutrophilia is a common feature of many chronic inflammatory lung diseases and is associated with disease progression, often regardless of the initiating cause. Neutrophils and their products are thought to be key mediators of the inflammatory changes in the airways of patients with chronic obstructive pulmonary disease (COPD) and have been shown to cause many of the pathological features associated with disease, including emphysema and mucus hypersecretion. Patients with COPD also have high rates of bacterial colonisation and recurrent infective exacerbations, suggesting that neutrophil host defence mechanisms are impaired, a concept supported by studies showing alterations to neutrophil migration, degranulation and reactive oxygen species production in cells isolated from patients with COPD. Although the role of neutrophils is best described in COPD, many of the pathological features of this disease are not unique to COPD and also feature in other chronic inflammatory airway diseases, including asthma, cystic fibrosis, alpha-1 anti-trypsin deficiency, and bronchiectasis. There is increasing evidence for immune cell dysfunction contributing to inflammation in many of these diseases, focusing interest on the neutrophil as a key driver of pulmonary inflammation and a potential therapeutic target than spans diseases. This review discusses the evidence for neutrophilic involvement in COPD and also considers their roles in alpha-1 anti-trypsin deficiency, bronchiectasis, asthma, and cystic fibrosis. We provide an in-depth assessment of the role of the neutrophil in each of these conditions, exploring recent advances in understanding, and finally discussing the possibility of common mechanisms across diseases.

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Section: Chronic Obstructive Pulmonary Diseasementioning

confidence: 99%

Understanding the role of neutrophils in chronic inflammatory airway disease

et al. 2019

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“…However, in COPD, alveolar macrophages are defective at phagocytosis of bacteria, fungal spores, and apoptotic epithelial cells [8][9][10]. Monocyte-derived macrophages (MDM) are used as a model of alveolar macrophages, and also carry the defect in phagocytosis observed in COPD [11].…”

Section: Introductionmentioning

confidence: 99%

Defective bacterial phagocytosis is associated with dysfunctional mitochondria in COPD macrophages

et al. 2019

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Increased reactive oxygen species (ROS) have been implicated in the pathophysiology of chronic obstructive pulmonary disease (COPD). This study examined the effect of exogenous and endogenous oxidative stress on macrophage phagocytosis in patients with COPD.Monocyte-derived macrophages (MDMs) were generated from non-smoker, smoker and COPD subjects, differentiated in either granulocyte macrophage-colony stimulating factor (G-Mφ) or macrophage-colony stimulating factor (M-Mφ). Alveolar macrophages were isolated from lung tissue or bronchoalveolar lavage fluid. Macrophages were incubated in ±200 µM H2O2 for 24 h, then exposed to fluorescently labelled Haemophilus influenzae or Streptococcus pneumoniae for 4 h, after which phagocytosis, mitochondrial ROS (mROS) and mitochondrial membrane potential (ΔΨm) were measured.Phagocytosis of bacteria was significantly decreased in both G-Mφ and M-Mφ from COPD patients compared with from non-smoker controls. In non-smokers and smokers, bacterial phagocytosis did not alter mROS or ΔΨm; however, in COPD, phagocytosis increased early mROS and decreased ΔΨm in both G-Mφ and M-Mφ. Exogenous oxidative stress reduced phagocytosis in non-smoker and COPD alveolar macrophages and non-smoker MDMs, associated with reduced mROS production.COPD macrophages show defective phagocytosis, which is associated with altered mitochondrial function and an inability to regulate mROS production. Targeting mitochondrial dysfunction may restore the phagocytic defect in COPD.

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“…For example, monocyte-derived macrophages exhibit defective phagocytic and proinflammatory cytokine response to A. fumigatus, leading to fungal germination and dissemination in patients with COPD. 21 Patients with DM are susceptible to candidiasis. Elevated blood glucose level creates a specific condition for intensive fungal colonization, 22 and DM per se is an independent predictor for biofilm-forming Candida bloodstream infection.…”

Section: Discussionmentioning

confidence: 99%

<p>Epidemiology and Mortality-Associated Factors of Invasive Fungal Disease in Elderly Patients: A 20-Year Retrospective Study from Southern China</p>

Gong

Wang

et al. 2020

IDR

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Introduction: Invasive fungal disease (IFD) is a life-threatening infection. The epidemiology and clinical features of IFD in the elderly population are less discussed. The aim of this study was to explore the epidemiology and mortality-associated factors for IFD in the elderly inpatients. Methods: A retrospective study enrolling 512 elderly inpatients from The First Affiliated Hospital of Sun Yat-sen University during the last two decades was performed. Results: The annual prevalence of IFD was 0.1-0.5%. Candidiasis was the most common (236/521, 45.3%). An increasing trend was observed in aspergillosis from 11.1% in year 1998 to 28.8% in year 2018. The common infective sites of candidiasis were abdominal cavity (83/236, 35.2%) and bloodstream (55/236, 23.3%). Invasive aspergillosis mainly developed in the sinus (74/149, 49.7%) and lung (65/149, 43.6%). Patients with diabetes mellitus (DM) (59/126, 46.8%), solid organ malignancy (84/114, 73.7%), chronic kidney disease (CKD) (40/62, 64.5%) or receiving operation (109/147, 74.1%) were prone to develop candidiasis, while aspergillosis was usually complicated in patients with chronic obstructive pulmonary disease (COPD) (25/51, 49.0%). The all-cause mortality rate was 25.9% (135/521), and patients aged ≥80 years were the riskiest (20/51, 39.2%). Lymphopenia (59.5% vs 17.3%, P<0.001) was significant in deceased patients with mold infection. Higher proportion of non-survivors with invasive candidiasis received central venous catheterization (CVC) (68.4% vs 40.6%, P<0.001) or indwelling urinary catheter (68.4% vs 46.3%, P=0.001). Conclusion: IFD is a life-threatening complication especially in the oldest-old. Surveillance on lymphopenia, prompt treatment and reduce invasive procedures could benefit the prognosis.

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Reduced Clearance of Fungal Spores by Chronic Obstructive Pulmonary Disease GM-CSF– and M-CSF–derived Macrophages

Cited by 19 publications

References 8 publications

Understanding the role of neutrophils in chronic inflammatory airway disease

Understanding the role of neutrophils in chronic inflammatory airway disease

Defective bacterial phagocytosis is associated with dysfunctional mitochondria in COPD macrophages

<p>Epidemiology and Mortality-Associated Factors of Invasive Fungal Disease in Elderly Patients: A 20-Year Retrospective Study from Southern China</p>

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