Alveolar macrophages of children suffering from recurrent infections of respiratory tract are less efficient in eliminating apoptotic neutrophils (original) (raw)

Recruitment and training of alveolar macrophages after pneumococcal pneumonia

JCI Insight, 2022

Recovery from pneumococcal pneumonia remodels the pool of alveolar macrophages so that they exhibit new surface marker profiles, transcriptomes, metabolomes, and responses to infection. Mechanisms mediating alveolar macrophage phenotypes after pneumococcal pneumonia have not been delineated. IFNg and its receptor on alveolar macrophages were essential for aspects but not all of the remodeled alveolar macrophage phenotype. IFNg was produced by CD4+ T cells plus other cells, and CD4+ cell depletion did not prevent alveolar macrophage remodeling. In mice infected or recovering from pneumococcus, monocytes were recruited to the lungs and the monocyte-derived macrophages developed characteristics of alveolar macrophages. CCR2 mediated the early monocyte recruitment but was not essential to development of the remodeled alveolar macrophage phenotype. Lineage tracing demonstrated that recovery from pneumococcal pneumonias converted the pool of alveolar macrophages from being primarily of embryonic origin to being primarily of adult hematopoietic stem cell origin. Alveolar macrophages of either origin demonstrated similar remodeled phenotypes, suggesting that ontogeny did not dictate phenotype. Altogether, our data reveal that the remodeled alveolar macrophage phenotype in lungs recovered from pneumococcal pneumonia results from a combination of new recruitment plus training of both the original cells and the new recruits.

Phagocyte extracellular traps in children with neutrophilic airway inflammation

ERJ Open Research, 2021

Childhood lung infection is often associated with prominent neutrophilic airway inflammation and excess production of proteases such as neutrophil elastase (NE). The mechanisms responsible for this inflammation are not well understood. One potentially relevant pathway is the production of extracellular traps by neutrophils (NETs) and macrophages (METs). The aim of this study was to measure NET and MET expression in children and the effect of deoxyribonculease (DNase) 1 and α1-antitrypsin (AAT) on this process.We studied 76 children (median age of 4.0 years) with cystic fibrosis or chronic cough who underwent investigational bronchoscopy. NETs, METs and neutrophil elastase activity in bronchoalveolar lavage (BAL) samples were measured using confocal microscopy and functional assays. The effects of DNase 1 and AAT on NET/MET expression and neutrophil elastase activity were examined in vitro.Both subject groups had airway neutrophilia with prominent BAL production of NETs with neutroph...

Influenza-induced bacterial infection: reduced number of airway macrophages

International Congress Series, 2001

Background: Influenza-induced bacterial superinfection causes morbidity and mortality associated with influenza epidemics. Certain bacterial species are commonly isolated from such infections, but it is unclear why certain bacterial species are preferentially affected. In this study, dual infection of influenza A virus (A/Qld/6/72) with various bacteria (H. influenzae, S. pneumoniae, S. aureus and P. aeruginosa) was studied in a mouse model of acute respiratory infection to assess the degree of bacterial superinfection, and effect on airway leukocytes. Methods: Mice were infected with A/Qld alone, bacteria alone, or a mixture of virus and bacteria. After 22 h mice were killed and broncho-alveolar lavage (BAL) fluid and lung tissue homogenates were assayed for live bacteria and BAL leukocyte subsets. Results: Influenza A/Qld caused a significant increase in H. influenzae and S. pneumoniae infection. Neutrophil (PMN) numbers were primarily related to the number of bacteria present. Macrophage numbers were reduced during mixed infection of A/Qld with H. influenzae or S. pneumoniae but were not affected by A/Qld plus P. aeruginosa or S. aureus infection. Conclusion: Differential effects of influenza/bacteria combinations on macrophages may partially account for preferential enhancement of particular bacterial infections during influenza infection. D

Impaired macrophage phagocytosis of bacteria in severe asthma

Respiratory research, 2014

Bacteria are frequently cultured from sputum samples of severe asthma patients suggesting a defect in bacterial clearance from the airway. We measured the capacity of macrophages from patients with asthma to phagocytose bacteria. Phagocytosis of fluorescently-labelled polystyrene beads, Haemophilus influenzae or Staphylococcus aureus by broncholaveolar lavage alveolar macrophages (AM) and by monocyte-derived macrophages (MDM) from non-asthmatics, mild-moderate and severe asthmatic patients was assessed using fluorimetry. There were no differences in phagocytosis of polystyrene beads by AMs or MDMs from any of the subject groups. There was reduced phagocytosis of Haemophilus influenzae and Staphylococcus aureus in MDMs from patients with severe asthma compared to non-severe asthma (p < 0.05 and p < 0.01, respectively) and healthy subjects (p < 0.01and p < 0.001, respectively). Phagocytosis of Haemophilus influenzae and Staphylococcus aureus by AM was also reduced in sever...

The inflammatory response in pneumonia

Intensivmedizin und Notfallmedizin, 1998

In normal conditions, alveolar macorphage (AM) is the main cell that respond against to bacteria that reach lower airways. However, if the microbial inoculum is too high or too virulent to be stopped by AM alone, these cells recruit polymorphonuclear neutrophils (PMN) into the alveoli from the vascular compartment. Cytokines, such as tumor necrosis factor-alpha (TNF-α), interleukin-1-beta (IL-1β), interleukin-6 (IL-6), and interleukin-8 (IL-8), secreted by the AM are able to attract PMN enhanced for phagocytosis are ready to destroy the invading pathogens. However, excessive cytokine production has delete-Die Entzündungsreaktion bei der Pneumonie Zusammenfassung Unter normalen Bedingungen ist der Alveolarmakrophage (AM) die wichtigste Zelle, die auf Bakterien reagiert, welche in die unteren Luftwege gelangen. Wenn das mikrobielle Inokulum zu stark oder zu virulent ist, um von AM allein aufgehalten zu werden, dann rekrutieren diese Zellen polymorphokernige Neutrophile (PMN) aus dem vaskulären Kompartiment in die Alveolen. Zytokine, IM 905

Small macrophages are present in early childhood respiratory disease

Journal of Cystic Fibrosis, 2012

Background: Recently, an established "small macrophage" phenotype has been observed in the sputum of patients with CF and COPD. However, little is known about the prevalence of this phenotype in the airways of young children. Since respiratory inflammation begins early in CF, we hypothesised that these small macrophages would be increased in paediatric CF bronchoalveolar lavage (BAL). Methods: Macrophage populations in CF and disease control BAL were assessed by multicolour flow cytometry. BAL inflammatory indices were collected as part of the AREST-CF programme. Results: Small macrophages were present in CF (n = 35, mean 36 ± 12% of BAL macrophages) but not significantly different to the respiratory disease controls (n = 7, mean 40 ± 21%). Number of small macrophages correlated significantly with number of BAL neutrophils (r = 0.44, p b 0.01) but not infection or IL-8. Conclusions: In paediatric patients small macrophages are not unique to CF, but their establishment as the dominant phenotype in adults may be due to chronicity of inflammation and infection.